Microvesicle - Knowledge

31: 707:. Although some of these microvesicle populations occur in the blood of healthy individuals and patients, there are obvious changes in number, cellular origin, and composition in various disease states. It has become clear that microvesicles play important roles in regulating the cellular processes that lead to disease pathogenesis. Moreover, because microvesicles are released following apoptosis or cell activation, they have the potential to induce or amplify disease processes. Some of the inflammatory and pathological conditions that microvesicles are involved in include 604:, which is essential for tumor survival and growth, occurs when endothelial cells proliferate to create a matrix of blood vessels that infiltrate the tumor, supplying the nutrients and oxygen necessary for tumor growth. A number of reports have demonstrated that tumor-associated microvesicles release proangiogenic factors that promote endothelial cell proliferation, angiogenesis, and tumor growth. Microvesicles shed by tumor cells and taken up by endothelial cells also facilitate angiogenic effects by transferring specific mRNAs and miRNAs. 452:)). The identification of RNA molecules in microvesicles supports the hypothesis that they are a biological vehicle for the transfer of nucleic acids and subsequently modulate the target cell's protein synthesis. Messenger RNA transported from one cell to another through microvesicles can be translated into proteins, conferring new function to the target cell. The discovery that microvesicles may shuttle specific mRNA and miRNA suggests that this may be a new mechanism of genetic exchange between cells. Exosomes produced by cells exposed to 247: 259:-derived particles that are released into the extracellular environment by the outward budding and fission of the plasma membrane. This budding process involves multiple signaling pathways including the elevation of intracellular calcium and reorganization of the cell's structural scaffolding. The formation and release of microvesicles involve contractile machinery that draws opposing membranes together before pinching off the membrane connection and launching the vesicle into the extracellular space. 470:

exchanging material between cells. This interaction ultimately leads to fusion with the target cell and release of the vesicles' components, thereby transferring bioactive molecules, lipids, genetic material, and proteins. The transfer of microvesicle components includes specific mRNAs and proteins, contributing to the proteomic properties of target cells. microvesicles can also transfer miRNAs that are known to regulate gene expression by altering mRNA turnover.

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some of which can be used as tumor biomarkers. Several tumor markers accessible as proteins in blood or urine have been used to screen and diagnose various types of cancer. In general, tumor markers are produced either by the tumor itself or by the body in response to the presence of cancer or some inflammatory conditions. If a tumor marker level is higher than normal, the patient is examined more closely to look for cancer or other conditions. For example,

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Krämer-Albers EM, Laitinen S, Lässer C, Lener T, Ligeti E, Linē A, Lipps G, Llorente A, Lötvall J, Manček-Keber M, Marcilla A, Mittelbrunn M, Nazarenko I, Nolte-'t Hoen EN, Nyman TA, O'Driscoll L, Olivan M, Oliveira C, Pállinger É, Del Portillo HA, Reventós J, Rigau M, Rohde E, Sammar M, Sánchez-Madrid F, Santarém N, Schallmoser K, Ostenfeld MS, Stoorvogel W, Stukelj R, Van der Grein SG, Vasconcelos MH, Wauben MH, De Wever O (2015).

649:(LMP1), which inhibits T-cell proliferation and prevents the removal of circulating tumor cells (CTCs). As a consequence, tumor cells can turn off T-cell responses or eliminate the antitumor immune cells altogether by releasing microvesicles. the combined use of microvesicles and 5-FU resulted in enhanced chemosensitivity of squamous cell carcinoma cells more than the use of either 5-FU or microvesicle alone 396:. Regardless of their cell type of origin, nearly all microvesicles contain proteins involved in membrane transport and fusion. They are surrounded by a phospholipid bilayer composed of several different lipid molecules. The protein content of each microvesicle reflects the origin of the cell from which it was released. For example, those released from antigen-presenting cells (APCs), such as 57:. In multicellular organisms, microvesicles and other EVs are found both in tissues (in the interstitial space between cells) and in many types of body fluids. Delimited by a phospholipid bilayer, microvesicles can be as small as the smallest EVs (30 nm in diameter) or as large as 1000 nm. They are considered to be larger, on average, than intracellularly-generated EVs known as 621:-insensitive cancer cells. Vesicles from these tumors contained nearly three times more cisplatin than those released from cisplatin-sensitive cells. For example, tumor cells can accumulate drugs into microvesicles. Subsequently, the drug-containing microvesicles are released from the cell into the extracellular environment, thereby mediating resistance to 979:

In addition to detecting cancer, it is possible to use microvesicles as biological markers to give prognoses for various diseases. Many types of neurological diseases are associated with increased level of specific types of circulating microvesicles. For example, elevated levels of phosphorylated tau

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malignancies, respectively. However, although they have proven clinical utility, none of these tumor markers are highly sensitive or specific. Clinical research data suggest that tumor-specific markers exposed on microvesicles are useful as a clinical tool to diagnose and monitor disease. Research is

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Tumor-associated microvesicles are abundant in the blood, urine, and other body fluids of patients with cancer, and are likely involved in tumor progression. They offer a unique opportunity to noninvasively access the wealth of biological information related to their cells of origin. The quantity and

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by modulating inflammatory cells. Additionally, microvesicles can induce clotting by binding to clotting factors or by inducing the expression of clotting factors in other cells. Circulating microvesicles isolated from cardiac surgery patients were found to be thrombogenic in both in vitro assays and

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In this form of signaling, the microvesicle does not fuse with the plasma membrane or engulfed by the target cell. Similar to the other mechanisms of signaling, the microvesicle has molecules on its surface that will interact specifically with its target cell. There are additional surface molecules,

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Microvesicles can be endocytosed upon binding to their targets, allowing for additional steps of regulation by the target cell. The microvesicle may fuse, integrating lipids and membrane proteins into the endosome while releasing its contents into the cytoplasm. Alternatively, the endosome may mature

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The lipid and protein content of microvesicles has been analyzed using various biochemical techniques. Microvesicles display a spectrum of enclosed molecules enclosed within the vesicles and their plasma membranes. Both the membrane molecular pattern and the internal contents of the vesicle depend on

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Yáñez-Mó M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, Colás E, Cordeiro-da Silva A, Fais S, Falcon-Perez JM, Ghobrial IM, Giebel B, Gimona M, Graner M, Gursel I, Gursel M, Heegaard NH, Hendrix A, Kierulf P, Kokubun K, Kosanovic M, Kralj-Iglic V,

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can mediate protective signals, reducing oxidative stress in recipient cells, a process which is proposed to depend on exosomal RNA transfer. These RNAs are specifically targeted to microvesicles, in some cases containing detectable levels of RNA that is not found in significant amounts in the donor

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The process of the formation of exosomes. 1. Cell undergoes endocytosis forming endocytic vesicles. 2. Endocytic vesicles fuse together forming an early endosome. 3. Endocytic cisterna matures into exocytic multivesicular body, during which membrane invaginations form exosomes. 4.Multivesicular body

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In addition to the proteins specific to the cell type of origin, some proteins are common to most microvesicles. For example, nearly all contain the cytoplasmic proteins tubulin, actin and actin-binding proteins, as well as many proteins involved in signal transduction, cell structure and motility,

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cells varies considerably compared with those released from normal cells. Thus, the concentration of plasma microvesicles with molecular markers indicative of the disease state may be used as an informative blood-based biosignature for cancer. Microvesicles express many membrane-bound proteins,

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Because the specific proteins, mRNAs, and miRNAs in microvesicles are highly variable, it is likely that these molecules are specifically packaged into vesicles using an active sorting mechanism. At this point, it is unclear exactly which mechanisms are involved in packaging soluble proteins and

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to insert drugs into microvesicles targeting specific cells, it is possible to target the drug very efficiently. This targeting can help by reducing necessary doses as well as prevent off-target side effects. They can target anti-inflammatory drugs to specific tissues. Additionally, circulating

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After cell stimulation, including apoptosis, a subsequent cytosolic Ca increase promotes the loss of phospholipid asymmetry of the plasma membrane, subsequent phosphatidylserine exposure, and a transient phospholipidic imbalance between the external leaflet at the expense of the inner leaflet,

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tumor, can be transferred to a non-aggressive population of tumor cells via microvesicles. After the oncogenic protein is transferred, the recipient cells become transformed and show characteristic changes in the expression levels of target genes. It is possible that transfer of other mutant

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Once released from their cell of origin, microvesicles interact specifically with cells they recognize by binding to cell-type specific, membrane-bound receptors. Because microvesicles contain a variety of surface molecules, they provide a mechanism for engaging different cell receptors and

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Once formed, both microvesicles and exosomes (collectively called extracellular vesicles) circulate in the extracellular space near the site of release, where they can be taken up by other cells or gradually deteriorate. In addition, some vesicles migrate significant distances by diffusion,

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Ghada A. Abd El Latif , Iman M. Aboushady and Dina Sabry Decreased VEGF and cyclin D1 genes expression enhances chemosensitivity of human squamous cell carcinoma cells to 5-fluorouracil and/or mesenchymal stem cells-derived microvesicles E.D.J. Vol. 65, 2, Pp 1217-1228 ; 2019. DOI:

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and deliver their cargo to neurons while not having an effect on muscle cells. The blood-brain barrier is typically a difficult obstacle to overcome when designing drugs, and microvesicles may be a means of overcoming it. Current research is looking into efficiently creating microvesicles

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is increased. Activation of platelets via collagen receptor GPVI stimulates the release of microvesicles from platelet cytoplasmic membranes. These microparticles are detectable at a high level in synovial fluid, and they promote joint inflammation by transporting proinflammatory cytokine

515:, on the surface of its target cell. Upon binding, the microvesicle can fuse with the plasma membrane. This results in the delivery of nucleotides and soluble proteins into the cytosol of the target cell as well as the integration of lipids and membrane proteins into its plasma membrane. 589:, may be a general mechanism by which malignant cells cause cancer growth at distant sites. Microvesicles from non-cancer cells can signal to cancer cells to become more aggressive. Upon exposure to microvesicles from tumor-associated macrophages, breast cancer cells become more invasive 848:

Evidence produced by independent research groups has demonstrated that microvesicles from the cells of healthy tissues, or selected miRNAs from these microvesicles, can be employed to reverse many tumors in pre-clinical cancer models, and may be used in combination with chemotherapy.

540:. This results in the ejection of the microvesicle back into the extracellular space or may result in the transportation of the microvesicle into a neighboring cell. This mechanism might explain the ability of microvesicle to cross biological barriers, such as the 557:

molecules on the surface of microvesicle can stimulate an immune response. Alternatively, there may be molecules on microvesicle surfaces that can recruit other proteins to form extracellular protein complexes that may be involved in signaling to the target cell.

123:). Platelets are activated by inflammation, infection, or injury, and after their activation microvesicles containing CD154 are released from platelets. CD154 is a crucial molecule in the development of T cell-dependent humoral immune response. CD154 2530:

Lakhal, S; Wood, MJ (October 2011). "Exosome nanotechnology: an emerging paradigm shift in drug delivery: exploitation of exosome nanovesicles for systemic in vivo delivery of RNAi heralds new horizons for drug delivery across biological barriers".

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Jansen, Felix; Yang, Xiaoyan; Hoyer, Friedrich Felix; Paul, Kathrin; Heiermann, Nadine; Becher, Marc Ulrich; Hussein, Nebal Abu; Kebschull, Moritz; Bedorf, Jörg; Franklin, Bernardo S.; Latz, Eicke; Nickenig, Georg; Werner, Nikos (14 Jun 2012).

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and invade surrounding tissues. Likewise, inhibiting MMP-2, MMP-9, and uPA prevents microvesicles from facilitating tumor metastasis. Matrix digestion can also facilitate angiogenesis, which is important for tumor growth and is induced by the

487:. During microvesicle production, the cell can concentrate and sort the signaling molecules which are released into the extracellular space upon microvesicle degradation. Dendritic cells, macrophage and microglia derived microvesicles contain 440:

are one of the most abundant protein families found in microvesicle membranes. Many of these proteins may be involved in the sorting and selection of specific cargos to be loaded into the lumen of the microvesicle or its membrane.

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to the area, resulting in the aggregation of cells. However, microvesicles also seem to be involved in a normal physiological response to disease, as there are increased levels of microvesicles that result from pathology.

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Dhondt, Bert; Geeurickx, Edward; Tulkens, Joeri; Van Deun, Jan; Vergauwen, Glenn; Lippens, Lien; Miinalainen, Ilkka; Rappu, Pekka; Heino, Jyrki; Ost, Piet; Lumen, Nicolaas; De Wever, Olivier; Hendrix, An (11 March 2020).

216:. Therefore, endothelial microparticles may be useful as an indicator or index of the functional state of the endothelium in disease, and may potentially play key roles in the pathogenesis of certain diseases, including 2282:

Valadi, Hadi; Ekström, Karin; Bossios, Apostolos; Sjöstrand, Margareta; Lee, James J; Lötvall, Jan O (2007). "Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells".

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Eldh M, Ekström K, Valadi H, Sjöstrand M, Olsson B, Jernås M, Lötvall J. Exosomes Communicate Protective Messages during Oxidative Stress; Possible Role of Exosomal Shuttle RNA. PLoS One. 2010 Dec 17;5(12):e15353.

289:, or an endocytic vesicle. In general, exosomes are formed by segregating the cargo (e.g., lipids, proteins, and nucleic acids) within the endosome. Once formed, the endosome combines with a structure known as a 616:

accumulate in microvesicles, the drug's cellular levels decrease. This can ultimately contribute to the process of drug resistance. Similar processes have been demonstrated in microvesicles released from

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Although circulating endothelial microparticles can be found in the blood of normal individuals, increased numbers of circulating endothelial microparticles have been identified in individuals with certain

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Aliotta, J.; Pereira, M.; Johnson, K.; De Paz, N.; Dooner, M.; Puente, N.; Ayala, C.; Brilliant, K.; Berz, D.; Lee, D.; Ramratnam, B.; McMillan, P. N.; Hixson, D. C.; Josic, D.; Quesenberry, P. J. (2010).

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Degradation of the extracellular matrix is a critical step in promoting tumor growth and metastasis. Tumor-derived microvesicles often carry protein-degrading enzymes, including matrix metalloproteinase 2

80:, and tissue regeneration. Microvesicles may also remove misfolded proteins, cytotoxic agents and metabolic waste from the cell. Changes in microvesicle levels may indicate diseases including cancer. 277:

Exosomes are membrane-covered vesicles, formed intracellularly are considered to be smaller than 100 nm. In contrast to microvesicles, which are formed through a process of membrane budding, or

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Hunter, M.; Ismail, N.; Zhang, X.; Aguda, B.; Lee, E.; Yu, L.; Xiao, T.; Schafer, J.; Lee, M.; Schmittgen, T. D.; Nana-Sinkam, S. P.; Jarjoura, D.; Marsh, C. B. (2008). Lo, Yuk Ming Dennis (ed.).

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Larkin, Samantha ET; Zeidan, Bashar; Taylor, Matthew G; Bickers, Bridget; Al-Ruwaili, Jamal; Aukim-Hastie, Claire; Townsend, Paul A (2010). "Proteomics in prostate cancer biomarker discovery".

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however, that can interact with receptor molecules which will interact with various signaling pathways. This mechanism of action can be used in processes such as antigen presentation, where

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Microvesicles and exosomes are formed and released by two slightly different mechanisms. These processes result in the release of intercellular signaling vesicles. Microvesicles are small,

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proteins can be used to diagnose patients in early stages of Alzheimer's. Additionally, it is possible to detect increased levels of CD133 in microvesicles of patients with epilepsy.

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are specifically sequestered in the inner leaflet of the membrane. The transbilayer lipid distribution is under the control of three phospholipidic pumps: an inward-directed pump, or

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Microvesicle budding takes place at unique locations on the cell membrane that are enriched with specific lipids and proteins reflecting their cellular origin. At these locations,

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from multivesicular bodies and the formation of exosomes. Another mechanism is budding of microvesicles directly from a plasma membrane. And the last one is cell death leading to

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and various forms of vasculitis. The endothelial microparticles in some of these disease states have been shown to have arrays of cell surface molecules reflecting a state of

76:. Like other EVs, they have been implicated in numerous physiologic processes, including anti-tumor effects, tumor immune suppression, metastasis, tumor-stroma interactions, 856:

to the surrounding healthy tissue. It leads to a change of healthy cell phenotype and creates a tumor-friendly environment. Microvesicles play an important role in tumor

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Lewin, Alfred; Yuan, Alex; Farber, Erica L.; Rapoport, Ana Lia; Tejada, Desiree; Deniskin, Roman; Akhmedov, Novrouz B.; Farber, Debora B. (2009). Lewin, Alfred (ed.).

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Pawlowski, Traci L.; Spetzler, David; Tinder, Teresa; Esmay, Paula; Conrad, Amber; Ellis, Phil; Kennedy, Patrick; Tyrell, Annemarie; et al. (April 20, 2010).

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which enable the identification of the endothelial origin of the microparticle, and allow it to be distinguished from microparticles from other cells, such as

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Pap, E.; Pállinger, É.; Pásztói, M.; Falus, A. (2009). "Highlights of a new type of intercellular communication: microvesicle-based information transfer".

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van der Pol, E; Böing, AN; Harrison, P; Sturk, A; Nieuwland, R (July 2012). "Classification, functions, and clinical relevance of extracellular vesicles".

1454:"Membrane Microvesicles as Actors in the Establishment of a Favorable Prostatic Tumoral Niche: A Role for Activated Fibroblasts and CX3CL1-CX3CR1 Axis" 1896:

Burnouf, T (October 2015). "An overview of the role of microparticles/microvesicles in blood components: Are they clinically beneficial or harmful?".

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After internalization of microvesicle via endocytosis, the endosome may move across the cell and fuse with the plasma membrane, a process called

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Microvesicles seem to be involved in a number of neurological diseases. Since they are involved in numerous vascular diseases and inflammation,

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Human Liver Stem Cell-Derived Microvesicles Inhibit Hepatoma Growth in SCID Mice by Delivering Antitumor MicroRNAs. Camussi et al; Stem Cells

2486:"Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery" 1304:"Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery" 3347: 785:

seem to be other diseases for which microvesicles are involved. Circulating microvesicles seem to have an increased level of phosphorylated

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the cellular origin and the molecular processes triggering their formation. Because microvesicles are not intact cells, they do not contain

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Hoyer, Friedrich Felix; Giesen, Meike Kristin; Nunes França, Carolina; Lütjohann, Dieter; Nickenig, Georg; Werner, Nikos (November 2012).

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in rats. Microvesicles isolated from healthy individuals did not have the same effects and may actually have a role in reducing clotting.

1405:"Microvesicle entry into marrow cells mediates tissue-specific changes in mRNA by direct delivery of mRNA and induction of transcription" 2880:

Müller, I; Klocke, A; Alex, M; Kotzsch, M; Luther, T; Morgenstern, E; Zieseniss, S; Zahler, S; Preissner, K; Engelmann, B (March 2003).

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Though initially dismissed as cellular debris, microvesicles may reflect the antigenic content of the cell of origin and have a role in

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Identifying and characterizing subpopulation of exosomes to provide the foundation for a novel exosome-based cancer diagnostic platform

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have a limited capability to control these cells. In the late stage, the extent of inflammation correlates with numbers of activated

293:(MVB). The MVB containing segregated endosomes ultimately fuses with the plasma membrane, resulting in exocytosis of the exosomes. 2986:"A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes" 760:

via numerous different pathways. These cells will then release more microvesicles, which have an additive effect. This can call

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Microvesicles are involved in cardiovascular disease initiation and progression. Microparticles derived from monocytes aggravate

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exposed to high glucose media release microvesicles containing tissue factor, having an angiogenic effect on endothelial cells.

2627:"Expulsion of small molecules in vesicles shed by cancer cells: association with gene expression and chemosensitivity profiles" 3305:

Kuslich, Christine; Pawlowski, Traci; Kimbrough, Jeff; Deng, Ta; Tinder, Teresa; Kim, Joon; Spetzler, David (April 18, 2010).

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Microvesicles (MVS) Derived From Adult Stem Cells For Use In The Therapeutic Treatment of a Tumor Disease. PCT/EP2011/052945

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Dhondt, Bert; Van Deun, Jan; Vermaerke, Silke; de Marco, Ario; Lumen, Nicolaas; De Wever, Olivier; Hendrix, An (June 2018).

1841:"Endothelial Microparticle Uptake in Target Cells Is Annexin I/Phosphatidylserine Receptor Dependent and Prevents Apoptosis" 3274:

Kuslich, Christine; Pawlowski, Traci L.; Deng, Ta; Tinder, Teresa; Kim, Joon; Kimbrough, Jeff; Spetzler, David (May 2010).

3090:"Unravelling the proteomic landscape of extracellular vesicles in prostate cancer by density-based fractionation of urine" 2232:

Simpson, Richard J.; Jensen, Søren S.; Lim, Justin W. E. (2008). "Proteomic profiling of exosomes: Current perspectives".

1607:"Platelet-mediated modulation of adaptive immunity: unique delivery of CD154 signal by platelet-derived membrane vesicles" 2135:

Hugel, B.; Martinez, M. C.; Kunzelmann, C.; Freyssinet, J. -M. (2005). "Membrane Microparticles: Two Sides of the Coin".

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Conversely, microvesicles processed from a tumor cell are involved in the transport of cancer proteins and in delivering

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There are three mechanisms which lead to release of vesicles into the extracellular space. First of these mechanisms is

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Kuslich, Christine; Pawlowski, Traci L.; Deng, Ta; Tinder, Teresa; Kim, Joon; Kimbrough, Jeff; Spetzler, David (2010).

2675: 1113:"Recent developments in the nomenclature, presence, isolation, detection and clinical impact of extracellular vesicles" 845:

also ongoing to determine if tumor-specific markers exposed on microvesicles are predictive for therapeutic response.

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Sun, D; Zhuang, X; Xiang, X; Liu, Y; Zhang, S; Liu, C; Barnes, S; Grizzle, W; Miller, D; Zhang, HG (September 2010).

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growth, and thus they prevent loss of blood. Moreover, they enhance immune response, since they express the molecule

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Kuslich, Christine; Pawlowski, Traci; Kimbrough, Jeff; Deng, Ta; Tinder, Teresa; Kim, Joon; Spetzler, David (2010).

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Castellana, D.; Zobairi, F.; Martinez, M. C.; Panaro, M. A.; Mitolo, V.; Freyssinet, J. -M.; Kunzelmann, C. (2009).

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Williams, C.; Royo, F.; Aizpurua-Olaizola, O.; Pazos, R.; Boons, G-J.; Reichardt, N-C.; Falcon-Perez, J.M. (2018).

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Microvesicles from various tumor types can express specific cell-surface molecules (e.g. FasL or CD95) that induce

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Biró, E; Sturk-Maquelin, KN; Vogel, GM; Meuleman, DG; Smit, MJ; Hack, CE; Sturk, A; Nieuwland, R (December 2003).

744:, an initiator of coagulation, is found in high levels within microvesicles, indicating their role in clotting. 3141:"Urinary extracellular vesicle biomarkers in urological cancers: From discovery towards clinical implementation" 2048:

Cocucci, Emanuele; Racchetti, Gabriella; Meldolesi, Jacopo (2009). "Shedding microvesicles: artefacts no more".

2626: 745: 408:, while microvesicles released from tumors contain proapoptotic molecules and oncogenic receptors (e.g. EGFR). 2792:"Microparticles as regulators of inflammation: novel players of cellular crosstalk in the rheumatic diseases" 17: 322: 1041: 688: 3411:

Nilsson, J; Skog, J; Nordstrand, A; Baranov, V; Mincheva-Nilsson, L; Breakefield, X O; Widmark, A (2009).

2833:"Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner" 716: 2576:"Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells" 3535: 3495: 2446:

Simons, Mikael; Raposo, Graça (2009). "Exosomes – vesicular carriers for intercellular communication".

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Shedden, Kerby; Xie, Xue Tao; Chandaroy, Parthapratim; Chang, Young Tae; Rosania, Gustavo R. (2003).

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Different cells can release microvesicles from the plasma membrane. Sources of microvesicles include

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Other than lipids and proteins, microvesicles are enriched with nucleic acids (e.g., messenger RNA (

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causing the degradation of the microvesicle and its contents, in which case the signal is ignored.

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Transmission electron micrograph of lead citrate stained microvesicles. Black bar is 100 nanometers

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Balaj, L.; Lessard, R.; Dai, L.; Cho, Y. J.; Pomeroy, S. L.; Breakefield, X. O.; Skog, J. (2011).

3540: 2934:"Development, cell differentiation, angiogenesis--microparticles and their roles in angiogenesis" 2881: 1002: 951: 869: 841: 285:. Exosomes are formed by invagination within a cell to create an intracellular vesicle called an 185: 3359: 1302:

Ratajczak, J.; Miekus, K.; Kucia, M.; Zhang, J.; Reca, R.; Dvorak, P.; Ratajczak, M. Z. (2006).

2882:"Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets" 989: 790: 708: 274:

are selectively incorporated into microvesicles and released into the surrounding environment.

61:. Microvesicles play a role in intercellular communication and can transport molecules such as 3263:. Proceedings of the 2010 American Society of Clinical Oncology Annual Meeting. Archived from 333: 3525: 3140: 1783:"Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle Production" 1558:"Glycosylation of extracellular vesicles: current knowledge, tools and clinical perspectives" 1494: 378: 328:

Under physiologic conditions, the plasma membrane of cells has an asymmetric distribution of

50: 3413:"Prostate cancer-derived urine exosomes: a novel approach to biomarkers for prostate cancer" 864:, which facilitate metastasis. They are also involved in intensification of the function of 3323: 2391: 1794: 1356: 1258: 915: 671: 511:

Proteins on the surface of the microvesicle will interact with specific molecules, such as

217: 3311:. Proceedings of the 101st Annual Meeting of the American Association for Cancer Research. 3264: 3243:. Proceedings of the 101st Annual Meeting of the American Association for Cancer Research. 2574:

Yang, M; Chen, J; Su, F; Yu, B; Su, F; Lin, L; Liu, Y; Huang, JD; Song, E (Sep 22, 2011).

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apoptosis and reduce the effectiveness of other immune cells. microvesicles released from

235:. Uptake of endothelial micoparticles is Annexin I/Phosphatidylserine receptor dependant. 8: 2734:"Monocytic microparticles promote atherogenesis by modulating inflammatory cells in mice" 1697:

Boulanger, Chantal M (March 2010). "Microparticles, vascular function and hypertension".

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Ratajczak, J; Miekus, K; Kucia, M; Zhang, J; Reca, R; Dvorak, P; Ratajczak, M Z (2006).

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Davizon, Pavela; López, José (September 2009). "Microparticles and thrombotic disease".

1360: 1262: 1247:"Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences" 232: 30: 3437: 3412: 3219: 3176: 3116: 3089: 3064: 3037: 3010: 2985: 2963: 2914: 2862: 2760: 2733: 2602: 2575: 2556: 2414: 2379: 2355: 2330: 2308: 2257: 2209: 2184: 2160: 2117: 2008: 1983: 1878: 1815: 1782: 1722: 1679: 1631: 1606: 1582: 1557: 1538: 1429: 1404: 1379: 1344: 1279: 1246: 1227: 1088: 1063: 919: 782: 724: 337: 3291: 2790:

Distler, JH; Pisetsky, DS; Huber, LC; Kalden, JR; Gay, S; Distler, O (November 2005).

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appoaches are sometimes called a “gesicle”, especially if used to package/deliver the

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Sprague DL, Elzey BD, Crist SA, Waldschmidt TJ, Jensen RJ, Ratliff TL (May 2008).

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and transcription. Most microvesicles contain the so-called "heat-shock proteins"

3156: 2404: 1710: 1667: 1622: 1420: 1369: 993: 885: 736: 704: 401: 389: 374: 267: 256: 177: 93: 483:

In some cases, the degradation of microvesicles is necessary for the release of

251:

fuses with the plasma membrane, releasing exosomes into the extracellular space.

2950: 2933: 2148: 1857: 1840: 1010: 997: 959: 931: 922:

characterized by inflammation of joints. In the early stage there are abundant

837: 500: 166: 89: 73: 2459: 2105: 2061: 1510: 1493:

Dhondt, Bert; Rousseau, Quentin; De Wever, Olivier; Hendrix, An (2016-06-11).

420:, which can facilitate interactions with cells of the immune system. Finally, 3519: 3276:"A sensitive exosome-based biosignature for the diagnosis of prostate cancer" 3164: 3054: 2592: 1934:

Van Doormaal, FF; Kleinjan, A; Di Nisio, M; Büller, HR; Nieuwland, R (2009).

1866: 1758: 1741: 1526: 968: 741: 356:, responsible for non-specific redistribution of lipids across the membrane. 329: 271: 209: 124: 62: 54: 1806: 1161:

Camussi G, Deregibus MC, Bruno S, Cantaluppi V, Biancone L (November 2010).

1111:

van der Pol, E.; Böing, A. N.; Gool, E. L.; Nieuwland, R. (1 January 2016).

625:

agents and resulting in significantly increased tumor growth, survival, and

3481: 3446: 3428: 3257:

A Sensitive exosome-based biosignature for the diagnosis of prostate cancer

3215: 3172: 3125: 3073: 3019: 2959: 2910: 2858: 2830: 2817: 2769: 2718: 2642: 2611: 2552: 2544: 2511: 2502: 2485: 2467: 2423: 2364: 2304: 2253: 2245: 2218: 2156: 2113: 2069: 2017: 1982:

Muralidharan-Chari V, Clancy JW, Sedgwick A, D'Souza-Schorey C (May 2010).

1951: 1917: 1874: 1824: 1767: 1718: 1675: 1640: 1591: 1534: 1518: 1479: 1438: 1388: 1329: 1320: 1303: 1288: 1223: 1188: 1138: 1097: 857: 786: 757: 712: 601: 537: 382: 370: 205: 77: 2901: 2346: 1345:"Detection of microRNA Expression in Human Peripheral Blood Microvesicles" 1215: 895:, so they can be an instrument for developing tumor vaccines. Circulating 3510: 3496:

Vesiclepedia—A database of molecules identified in extracellular vesicles

3472: 1079: 963: 947: 939: 904: 761: 700: 613: 421: 282: 213: 163: 111:

Platelets play an important role in maintaining hemostasis: they promote

101: 3001: 1179: 1162: 1006:

synthetically, or isolating them from patient or engineered cell lines.

946:

destruction, because they have the ability to transform themselves into

1999: 1270: 1036: 873: 765: 696: 626: 353: 318: 278: 3207: 3035: 2808: 2791: 2789: 1129: 1112: 246: 1163:"Exosomes/microvesicles as a mechanism of cell-to-cell communication" 955: 943: 881: 816: 692: 667: 618: 224: 97: 3317:"Circulating exosomes are a robust biosignature for prostate cancer" 2296: 687:

The release of microvesicles has been shown from endothelial cells,

360:

leading to budding of the plasma membrane and microvesicle release.

1495:"Function of extracellular vesicle-associated miRNAs in metastasis" 853: 798: 720: 525: 512: 349: 345: 286: 193: 189: 140: 112: 105: 66: 1933: 1742:"Evaluation of plasma endothelial microparticles in pre-eclampsia" 1555: 2134: 892: 778: 492: 397: 201: 181: 2879: 2731: 3138: 1451: 1160: 825: 821: 638: 581: 144: 3456:"Microvesicles: messengers and mediators of tumor progression" 3086: 2331:"Extracellular vesicles: Exosomes, microvesicles, and friends" 3314: 3308:

Plasma exosomes are a robust biosignature for prostate cancer

3304: 2690: 2281: 2185:"Exosome Function: From Tumor Immunology to Pathogen Biology" 1492: 1201: 1110: 896: 877: 794: 670:). By releasing these proteases, tumor cells can degrade the 663: 659: 449: 417: 413: 306: 302: 170: 120: 116: 3410: 3236: 3145:

The International Journal of Biochemistry & Cell Biology

3038:"Microvesicles: novel biomarkers for neurological disorders" 2380:"Transfer of MicroRNAs by Embryonic Stem Cell Microvesicles" 1604: 1060: 1401: 1014: 923: 872:, because microvesicles released from a tumor cell contain 586: 445: 437: 433: 429: 3500: 3273: 3253: 2983: 1653: 926:

cells producing proinflammatory cytokines IL-17A, IL-17F,

3193: 2483: 2047: 1301: 927: 910: 900: 425: 184:. The membrane of the endothelial microparticle contains 136: 132: 3036:

Colombo, E; Borgiani, B; Verderio, C; Furlan, R (2012).

2691:

Vanwijk, M; Vanbavel, E; Sturk, A; Nieuwland, R (2003).

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and in the degradation of matrix due to the presence of

647:

the immune-suppressing protein latent membrane protein-1

571: 3501:

ExoCarta—A database of molecules identified in exosomes

2377: 632: 238:

Microparticles are derived from many other cell types.

3511:

Resource on the detection of circulating microvesicles

3454:

Al-Nedawi, Khalid; Meehan, Brian; Rak, Janusz (2009).

1342: 607: 223:

Endothelial microparticles have been found to prevent

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molecular composition of microvesicles released from

1696: 1238: 580:, which is located in a specific type of aggressive 2328: 1837: 942:that contribute to joint inflammation and bone and 682: 297:ultimately appearing in biological fluids such as 3505: 3453: 2938:Arteriosclerosis, Thrombosis, and Vascular Biology 2670:. San Diego, CA: Academic Press. pp. 453–67. 1845:Arteriosclerosis, Thrombosis, and Vascular Biology 1244: 2183:Schorey, Jeffrey S.; Bhatnagar, Sanchita (2008). 974: 3517: 3506:International Society for Extracellular Vesicles 2231: 2182: 1027:International Society for Extracellular Vesicles 988:Circulating microvesicles may be useful for the 907:can be potential markers for tumor diagnostics. 756:Microvesicles contain cytokines that can induce 3247: 3230: 3031: 3029: 2979: 2977: 2525: 2523: 2521: 2479: 2477: 2324: 2322: 2277: 2275: 2273: 2271: 2178: 2176: 2174: 2087: 2085: 2083: 2081: 2079: 2043: 2041: 2039: 2037: 2035: 2033: 2031: 2029: 2027: 1977: 1975: 1973: 1971: 1969: 1967: 1965: 1963: 1961: 1929: 1927: 1733: 3298: 2529: 1774: 1699:Current Opinion in Nephrology and Hypertension 983: 547: 2659: 1690: 652: 150: 3187: 3026: 2974: 2931: 2684: 2618: 2518: 2474: 2445: 2439: 2371: 2319: 2268: 2225: 2171: 2076: 2024: 1958: 1924: 1598: 666:, and urokinase-type plasminogen activator ( 325:. These are all energy-requiring processes. 2693:"Microparticles in cardiovascular diseases" 1780: 1647: 2785: 2783: 2781: 2779: 2738:Journal of Cellular and Molecular Medicine 1195: 473: 3471: 3436: 3115: 3105: 3063: 3053: 3009: 2949: 2900: 2848: 2807: 2759: 2749: 2708: 2665: 2601: 2591: 2501: 2413: 2403: 2354: 2329:Raposo, G; Stoorvogel, W (Feb 18, 2013). 2208: 2007: 1856: 1814: 1781:Boilard, E.; et al. (January 2010). 1757: 1630: 1581: 1469: 1428: 1378: 1368: 1319: 1278: 1178: 1156: 1154: 1152: 1150: 1148: 1128: 1087: 772: 730: 596: 404:, are enriched in proteins necessary for 388:Microvesicle membranes consist mainly of 83: 804: 312: 245: 233:mitogen-activated protein kinase (MKP)-1 29: 2776: 1936:"Cell-derived microvesicles and cancer" 1895: 1054: 950:that destroy bone tissue. Synthesis of 561: 464: 241: 14: 3518: 1739: 1145: 911:Microvesicles and Rheumatoid arthritis 809: 3322:. Caris Life Sciences. Archived from 2837:Journal of Thrombosis and Haemostasis 1117:Journal of Thrombosis and Haemostasis 891:Tumor microvesicles also carry tumor 868:and in the induction of apoptosis of 572:Promoting aggressive tumor phenotypes 363: 227:in recipient cells by inhibiting the 1104: 633:Interference with antitumor immunity 169:and can be found circulating in the 3372:"CORDIS | European Commission" 1940:The Netherlands Journal of Medicine 608:Involvement in multidrug resistance 281:, exosomes are initially formed by 24: 3404: 2932:Shai, E; Varon, D (January 2011). 1009:Microvesicles used in therapeutic 880:. They prevent differentiation of 518: 461:nucleic acids into microvesicles. 208:and cardiovascular disorders, and 143:. Microvesicles can also transfer 25: 3552: 3489: 3292:10.1200/jco.2010.28.15_suppl.4636 3094:Journal of Extracellular Vesicles 1562:Journal of Extracellular Vesicles 1032:Journal of Extracellular Vesicles 793:. Similarly, increased levels of 503:using this mechanism of release. 2850:10.1046/j.1538-7836.2003.00456.x 2751:10.1111/j.1582-4934.2012.01595.x 2201:10.1111/j.1600-0854.2008.00734.x 992:to very specific targets. Using 832:have been used to help diagnose 683:Cellular Origin of Microvesicles 176:The microparticle consists of a 53:(EV) that are released from the 3389: 3364: 3352: 3340: 3132: 3080: 2925: 2873: 2824: 2725: 2668:Platelet-Derived Microparticles 2649: 2567: 2448:Current Opinion in Cell Biology 2430: 2128: 1889: 1831: 1549: 1486: 751: 544:, by moving from cell to cell. 531: 348:; an outward-directed pump, or 1445: 1395: 1336: 1295: 975:Biological markers for disease 612:When anticancer drugs such as 478: 180:surrounding a small amount of 147:and molecules CD41 and CXCR4. 69:, and proteins between cells. 13: 1: 3107:10.1080/20013078.2020.1736935 2710:10.1016/S0008-6363(03)00367-5 1910:10.1016/j.transci.2015.10.010 1656:Current Opinion in Hematology 1574:10.1080/20013078.2018.1442985 1471:10.1158/0008-5472.CAN-08-1946 1047: 1001:microvesicles can bypass the 27:Type of extracellular vesicle 3280:Journal of Clinical Oncology 3157:10.1016/j.biocel.2018.04.009 2405:10.1371/journal.pone.0004722 1711:10.1097/MNH.0b013e32833640fd 1668:10.1097/MOH.0b013e32832ea49c 1623:10.1182/blood-2007-06-097410 1421:10.1016/j.exphem.2010.01.002 1370:10.1371/journal.pone.0003694 1042:Membrane vesicle trafficking 689:vascular smooth muscle cells 679:of RNAs from microvesicles. 7: 3396:"gesicle" on wiktionary.org 3196:Expert Review of Proteomics 2335:The Journal of Cell Biology 1020: 984:Mechanism for drug delivery 717:neurodegenerative disorders 548:Contact dependent signaling 127:are incapable of producing 10: 3557: 2951:10.1161/atvbaha.109.200980 2149:10.1152/physiol.00029.2004 1858:10.1161/ATVBAHA.112.253229 930:, IL-21, and IL-22 in the 695:, white blood cells (e.g. 653:Impact on tumor metastasis 156:Endothelial microparticles 151:Endothelial microparticles 3417:British Journal of Cancer 2460:10.1016/j.ceb.2009.03.007 2106:10.1007/s00011-008-8210-7 2062:10.1016/j.tcb.2008.11.003 1511:10.1007/s00441-016-2430-x 566: 506: 489:proinflammatory cytokines 385:with its associated DNA. 231:pathway via inactivating 3055:10.3389/fphys.2012.00063 2796:Arthritis and Rheumatism 2593:10.1186/1476-4598-10-117 1759:10.1177/0300060513504362 1499:Cell and Tissue Research 936:regulatory T-lymphocytes 866:regulatory T-lymphocytes 342:phosphatidylethanolamine 3042:Frontiers in Physiology 2697:Cardiovascular Research 2656:10.21608/EDJ.2019.72197 1988:Journal of Cell Science 1807:10.1126/science.1181928 1409:Experimental Hematology 1204:Pharmacological Reviews 952:reactive oxygen species 870:cytotoxic T-lymphocytes 576:The oncogenic receptor 474:Mechanisms of signaling 214:endothelial dysfunction 188:and other cell surface 162:that are released from 3429:10.1038/sj.bjc.6605058 2545:10.1002/bies.201100076 2503:10.1038/sj.leu.2404132 2246:10.1002/pmic.200800109 2050:Trends in Cell Biology 1321:10.1038/sj.leu.2404132 918:is a chronic systemic 773:Neurological disorders 731:Cardiovascular disease 709:cardiovascular disease 597:Promoting angiogenesis 252: 84:Formation and contents 35: 2902:10.1096/fj.02-0574fje 2666:Nieuwland, R (2012). 2347:10.1083/jcb.201211138 2094:Inflammation Research 1251:Nature Communications 1216:10.1124/pr.112.005983 805:Clinical applications 746:Renal mesangial cells 379:endoplasmic reticulum 313:Mechanism of shedding 249: 51:extracellular vesicle 33: 3473:10.4161/cc.8.13.8988 1167:Kidney International 1080:10.3402/jev.v4.27066 1068:J Extracell Vesicles 916:Rheumatoid arthritis 797:are an indicator of 672:extracellular matrix 562:Relevance in disease 465:Role on target cells 424:proteins, including 242:Process of formation 218:rheumatoid arthritis 3002:10.1038/mt.2010.105 2396:2009PLoSO...4.4722Y 2285:Nature Cell Biology 1799:2010Sci...327..580B 1740:Ling L (Feb 2014). 1361:2008PLoSO...3.3694H 1263:2011NatCo...2..180B 1180:10.1038/ki.2010.278 1003:blood–brain barrier 810:Detection of cancer 791:Alzheimer's disease 789:during early stage 677:horizontal transfer 585:oncogenes, such as 542:blood brain barrier 485:signaling molecules 299:cerebrospinal fluid 291:multivesicular body 3313:Also published as 3286:(15 suppl): 4636. 3272:Also published as 2000:10.1242/jcs.064386 1994:(Pt 10): 1603–11. 1898:Transfus Apher Sci 1271:10.1038/ncomms1180 920:autoimmune disease 783:multiple sclerosis 725:rheumatic diseases 364:Molecular contents 338:phosphatidylserine 334:aminophospholipids 323:apoptotic blebbing 253: 104:, tumor cells and 36: 3536:Medical diagnosis 3208:10.1586/epr.09.89 2990:Molecular Therapy 2809:10.1002/art.21350 2744:(11): 2777–2788. 1793:(5965): 580–583. 1130:10.1111/jth.13190 990:delivery of drugs 497:endothelial cells 406:adaptive immunity 394:membrane proteins 139:as a response to 16:(Redirected from 3548: 3485: 3475: 3450: 3440: 3398: 3393: 3387: 3386: 3384: 3383: 3374:. Archived from 3368: 3362: 3360:Available online 3356: 3350: 3348:Available online 3344: 3338: 3337: 3335: 3334: 3328: 3321: 3312: 3302: 3296: 3295: 3271: 3269: 3262: 3251: 3245: 3244: 3234: 3228: 3227: 3191: 3185: 3184: 3136: 3130: 3129: 3119: 3109: 3084: 3078: 3077: 3067: 3057: 3033: 3024: 3023: 3013: 2981: 2972: 2971: 2953: 2929: 2923: 2922: 2904: 2886: 2877: 2871: 2870: 2852: 2828: 2822: 2821: 2811: 2787: 2774: 2773: 2763: 2753: 2729: 2723: 2722: 2712: 2688: 2682: 2681: 2663: 2657: 2653: 2647: 2646: 2622: 2616: 2615: 2605: 2595: 2580:Molecular Cancer 2571: 2565: 2564: 2527: 2516: 2515: 2505: 2481: 2472: 2471: 2443: 2437: 2434: 2428: 2427: 2417: 2407: 2375: 2369: 2368: 2358: 2326: 2317: 2316: 2279: 2266: 2265: 2229: 2223: 2222: 2212: 2180: 2169: 2168: 2132: 2126: 2125: 2089: 2074: 2073: 2045: 2022: 2021: 2011: 1979: 1956: 1955: 1931: 1922: 1921: 1893: 1887: 1886: 1860: 1851:(8): 1925–1935. 1835: 1829: 1828: 1818: 1778: 1772: 1771: 1761: 1737: 1731: 1730: 1694: 1688: 1687: 1651: 1645: 1644: 1634: 1602: 1596: 1595: 1585: 1553: 1547: 1546: 1490: 1484: 1483: 1473: 1449: 1443: 1442: 1432: 1399: 1393: 1392: 1382: 1372: 1340: 1334: 1333: 1323: 1299: 1293: 1292: 1282: 1242: 1236: 1235: 1199: 1193: 1192: 1182: 1158: 1143: 1142: 1132: 1108: 1102: 1101: 1091: 1058: 899:and segments of 862:metalloproteases 842:gastrointestinal 623:chemotherapeutic 454:oxidative stress 448:) and microRNA ( 49:) are a type of 21: 3556: 3555: 3551: 3550: 3549: 3547: 3546: 3545: 3516: 3515: 3492: 3407: 3405:Further reading 3402: 3401: 3394: 3390: 3381: 3379: 3370: 3369: 3365: 3357: 3353: 3345: 3341: 3332: 3330: 3326: 3319: 3303: 3299: 3267: 3260: 3252: 3248: 3235: 3231: 3192: 3188: 3137: 3133: 3085: 3081: 3034: 3027: 2982: 2975: 2930: 2926: 2884: 2878: 2874: 2829: 2825: 2802:(11): 3337–48. 2788: 2777: 2730: 2726: 2689: 2685: 2678: 2664: 2660: 2654: 2650: 2631:Cancer Research 2623: 2619: 2572: 2568: 2528: 2519: 2482: 2475: 2444: 2440: 2435: 2431: 2376: 2372: 2327: 2320: 2297:10.1038/ncb1596 2280: 2269: 2240:(19): 4083–99. 2230: 2226: 2181: 2172: 2133: 2129: 2090: 2077: 2046: 2025: 1980: 1959: 1932: 1925: 1894: 1890: 1836: 1832: 1779: 1775: 1738: 1734: 1695: 1691: 1652: 1648: 1617:(10): 5028–36. 1603: 1599: 1554: 1550: 1519:1854/LU-7250365 1491: 1487: 1458:Cancer Research 1450: 1446: 1400: 1396: 1341: 1337: 1300: 1296: 1243: 1239: 1200: 1196: 1159: 1146: 1109: 1105: 1059: 1055: 1050: 1023: 994:electroporation 986: 977: 913: 886:dendritic cells 812: 807: 775: 754: 737:atherosclerosis 733: 705:red blood cells 685: 655: 635: 610: 599: 574: 569: 564: 550: 534: 521: 519:Internalization 509: 481: 476: 467: 402:dendritic cells 390:membrane lipids 366: 315: 257:plasma membrane 244: 178:plasma membrane 153: 94:blood platelets 86: 28: 23: 22: 15: 12: 11: 5: 3554: 3544: 3543: 3541:Nanotechnology 3538: 3533: 3528: 3514: 3513: 3508: 3503: 3498: 3491: 3490:External links 3488: 3487: 3486: 3466:(13): 2014–8. 3451: 3406: 3403: 3400: 3399: 3388: 3363: 3351: 3339: 3297: 3270:on 2011-07-10. 3246: 3229: 3186: 3131: 3100:(1): 1736935. 3079: 3025: 2996:(9): 1606–14. 2973: 2924: 2872: 2843:(12): 2561–8. 2823: 2775: 2724: 2683: 2677:978-0123878373 2676: 2658: 2648: 2637:(15): 4331–7. 2617: 2566: 2539:(10): 737–41. 2517: 2473: 2438: 2429: 2370: 2318: 2267: 2224: 2170: 2127: 2075: 2023: 1957: 1923: 1888: 1830: 1773: 1732: 1705:(2): 177–180. 1689: 1662:(5): 334–341. 1646: 1597: 1568:(1): 1442985. 1548: 1505:(3): 621–641. 1485: 1464:(3): 785–793. 1444: 1415:(3): 233–245. 1394: 1335: 1314:(5): 847–856. 1294: 1237: 1210:(3): 676–705. 1194: 1144: 1103: 1052: 1051: 1049: 1046: 1045: 1044: 1039: 1034: 1029: 1022: 1019: 1011:genome editing 998:centrifugation 985: 982: 976: 973: 960:prostaglandins 932:synovial fluid 912: 909: 811: 808: 806: 803: 774: 771: 753: 750: 732: 729: 684: 681: 654: 651: 645:cells express 643:lymphoblastoma 634: 631: 609: 606: 598: 595: 573: 570: 568: 565: 563: 560: 549: 546: 533: 530: 520: 517: 508: 505: 501:growth factors 480: 477: 475: 472: 466: 463: 365: 362: 352:; and a lipid 314: 311: 243: 240: 152: 149: 90:megakaryocytes 85: 82: 74:cell signaling 47:microparticles 26: 9: 6: 4: 3: 2: 3553: 3542: 3539: 3537: 3534: 3532: 3529: 3527: 3524: 3523: 3521: 3512: 3509: 3507: 3504: 3502: 3499: 3497: 3494: 3493: 3483: 3479: 3474: 3469: 3465: 3461: 3457: 3452: 3448: 3444: 3439: 3434: 3430: 3426: 3422: 3418: 3414: 3409: 3408: 3397: 3392: 3378:on 2008-03-28 3377: 3373: 3367: 3361: 3355: 3349: 3343: 3329:on 2016-03-04 3325: 3318: 3310: 3309: 3301: 3293: 3289: 3285: 3281: 3277: 3266: 3259: 3258: 3250: 3242: 3241: 3233: 3225: 3221: 3217: 3213: 3209: 3205: 3202:(1): 93–102. 3201: 3197: 3190: 3182: 3178: 3174: 3170: 3166: 3162: 3158: 3154: 3150: 3146: 3142: 3135: 3127: 3123: 3118: 3113: 3108: 3103: 3099: 3095: 3091: 3083: 3075: 3071: 3066: 3061: 3056: 3051: 3047: 3043: 3039: 3032: 3030: 3021: 3017: 3012: 3007: 3003: 2999: 2995: 2991: 2987: 2980: 2978: 2969: 2965: 2961: 2957: 2952: 2947: 2943: 2939: 2935: 2928: 2920: 2916: 2912: 2908: 2903: 2898: 2895:(3): 476–78. 2894: 2890: 2889:FASEB Journal 2883: 2876: 2868: 2864: 2860: 2856: 2851: 2846: 2842: 2838: 2834: 2827: 2819: 2815: 2810: 2805: 2801: 2797: 2793: 2786: 2784: 2782: 2780: 2771: 2767: 2762: 2757: 2752: 2747: 2743: 2739: 2735: 2728: 2720: 2716: 2711: 2706: 2703:(2): 277–87. 2702: 2698: 2694: 2687: 2679: 2673: 2669: 2662: 2652: 2644: 2640: 2636: 2632: 2628: 2621: 2613: 2609: 2604: 2599: 2594: 2589: 2585: 2581: 2577: 2570: 2562: 2558: 2554: 2550: 2546: 2542: 2538: 2534: 2526: 2524: 2522: 2513: 2509: 2504: 2499: 2496:(5): 847–56. 2495: 2491: 2487: 2480: 2478: 2469: 2465: 2461: 2457: 2454:(4): 575–81. 2453: 2449: 2442: 2433: 2425: 2421: 2416: 2411: 2406: 2401: 2397: 2393: 2389: 2385: 2381: 2374: 2366: 2362: 2357: 2352: 2348: 2344: 2341:(4): 373–83. 2340: 2336: 2332: 2325: 2323: 2314: 2310: 2306: 2302: 2298: 2294: 2290: 2286: 2278: 2276: 2274: 2272: 2263: 2259: 2255: 2251: 2247: 2243: 2239: 2235: 2228: 2220: 2216: 2211: 2206: 2202: 2198: 2195:(6): 871–81. 2194: 2190: 2186: 2179: 2177: 2175: 2166: 2162: 2158: 2154: 2150: 2146: 2142: 2138: 2131: 2123: 2119: 2115: 2111: 2107: 2103: 2099: 2095: 2088: 2086: 2084: 2082: 2080: 2071: 2067: 2063: 2059: 2055: 2051: 2044: 2042: 2040: 2038: 2036: 2034: 2032: 2030: 2028: 2019: 2015: 2010: 2005: 2001: 1997: 1993: 1989: 1985: 1978: 1976: 1974: 1972: 1970: 1968: 1966: 1964: 1962: 1953: 1949: 1946:(7): 266–73. 1945: 1941: 1937: 1930: 1928: 1919: 1915: 1911: 1907: 1904:(2): 137–45. 1903: 1899: 1892: 1884: 1880: 1876: 1872: 1868: 1864: 1859: 1854: 1850: 1846: 1842: 1834: 1826: 1822: 1817: 1812: 1808: 1804: 1800: 1796: 1792: 1788: 1784: 1777: 1769: 1765: 1760: 1755: 1751: 1747: 1746:J Int Med Res 1743: 1736: 1728: 1724: 1720: 1716: 1712: 1708: 1704: 1700: 1693: 1685: 1681: 1677: 1673: 1669: 1665: 1661: 1657: 1650: 1642: 1638: 1633: 1628: 1624: 1620: 1616: 1612: 1608: 1601: 1593: 1589: 1584: 1579: 1575: 1571: 1567: 1563: 1559: 1552: 1544: 1540: 1536: 1532: 1528: 1524: 1520: 1516: 1512: 1508: 1504: 1500: 1496: 1489: 1481: 1477: 1472: 1467: 1463: 1459: 1455: 1448: 1440: 1436: 1431: 1426: 1422: 1418: 1414: 1410: 1406: 1398: 1390: 1386: 1381: 1376: 1371: 1366: 1362: 1358: 1355:(11): e3694. 1354: 1350: 1346: 1339: 1331: 1327: 1322: 1317: 1313: 1309: 1305: 1298: 1290: 1286: 1281: 1276: 1272: 1268: 1264: 1260: 1256: 1252: 1248: 1241: 1233: 1229: 1225: 1221: 1217: 1213: 1209: 1205: 1198: 1190: 1186: 1181: 1176: 1173:(9): 838–48. 1172: 1168: 1164: 1157: 1155: 1153: 1151: 1149: 1140: 1136: 1131: 1126: 1122: 1118: 1114: 1107: 1099: 1095: 1090: 1085: 1081: 1077: 1073: 1069: 1065: 1057: 1053: 1043: 1040: 1038: 1035: 1033: 1030: 1028: 1025: 1024: 1018: 1017:RNP complex. 1016: 1012: 1007: 1004: 999: 995: 991: 981: 972: 970: 965: 961: 957: 953: 949: 945: 941: 937: 933: 929: 925: 921: 917: 908: 906: 902: 898: 894: 889: 887: 883: 879: 875: 871: 867: 863: 859: 855: 850: 846: 843: 839: 835: 831: 827: 823: 818: 802: 800: 796: 792: 788: 784: 780: 770: 767: 763: 759: 749: 747: 743: 742:Tissue factor 738: 728: 726: 722: 718: 714: 710: 706: 702: 698: 694: 690: 680: 678: 673: 669: 665: 661: 650: 648: 644: 640: 630: 628: 624: 620: 615: 605: 603: 594: 592: 588: 583: 579: 559: 556: 545: 543: 539: 529: 527: 516: 514: 504: 502: 498: 494: 490: 486: 471: 462: 458: 455: 451: 447: 442: 439: 435: 431: 427: 423: 419: 415: 409: 407: 403: 399: 395: 391: 386: 384: 380: 376: 372: 361: 357: 355: 351: 347: 343: 339: 335: 331: 330:phospholipids 326: 324: 320: 310: 308: 304: 300: 294: 292: 288: 284: 280: 275: 273: 272:nucleic acids 269: 265: 260: 258: 248: 239: 236: 234: 230: 226: 221: 219: 215: 211: 210:pre-eclampsia 207: 203: 197: 195: 191: 187: 183: 179: 174: 172: 168: 165: 161: 157: 148: 146: 142: 138: 134: 130: 126: 125:knockout mice 122: 118: 114: 109: 107: 103: 99: 95: 91: 81: 79: 75: 70: 68: 64: 60: 56: 55:cell membrane 52: 48: 44: 40: 39:Microvesicles 32: 19: 18:Microvesicles 3526:Cell biology 3463: 3459: 3420: 3416: 3391: 3380:. 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