Posts Tagged: cell-derived microparticles

Extracellular Vesicles in Angiogenesis

Extracellular Vesicles in Angiogenesis

Dilyana Todorova, Stéphanie Simoncini, Romaric Lacroix, Florence Sabatier, Françoise Dignat-George

Mechanisms involved in the modulation of Angiogenesis by endothelial cell (EC)–derived extracellular vesicles (EVs). EC release EVs rich in micro-RNA such as miR-214 and miR-126, that are transferred to recipient EC and induce proangiogenic signaling. EVs contain functional matrix metalloproteinases that facilitate angiogenesis through the degradation of components of the extracellular matrix. Dll4 is transferred to EC by the EVs and induces Notch receptor internalization and tip cell formation. EVs bear, at their surface, a tissue factor that interacts with β1 integrin and induces Rac1-ERK1/2-ETS1 signaling, leading to the increased secretion of CCL2. EVs transport the complex uPA/uPAR, which stimulates angiogenesis through plasmin generation. The phosphatidylserine present on the surface of the EVs interacts with CD36 and induces Fyn kinase signaling, which leads to increased oxidative stress and the inhibition of angiogenesis. ATM indicates ataxia telangiectasia mutated; CCl2, chemokine c-c motif ligand 2; Dll4, Delta-like 4; ECM, extracellular matrix; ERK1/2, extracellular signal-related kinase 1 and 2; ETS1, avian erythroblastosis virus E26 homolog-1; IL-3R, interleukin-3 receptor; MMPs, matrix metalloproteinases; NotchR, Notch receptor; PS, phosphatidylserine; Rac1, Ras-related C3 botulinum toxin substrate 1; ROS, reactive oxygen species; TF, tissue factor; TIMPS, tissue inhibitor of metalloproteinases; uPA, urokinase plasminogen activator; and uPAR, urokinase plasminogen activator receptor. [Powerpoint File]

Extracellular Vesicles in Angiogenesis

Extracellular Vesicles in Angiogenesis

Dilyana Todorova, Stéphanie Simoncini, Romaric Lacroix, Florence Sabatier, Françoise Dignat-George

Mechanisms involved in the modulation of Angiogenesis by platelet-derived extracellular vesicles (EVs). Platelet-derived EVs contain various growth factors and chemokines that induce proangiogenic signaling in endothelial cell (EC). Spingosine-1-phosphate (S1P1), present on the EV surface, induces PI3K activation and, together with VEGF and bFGF, promotes angiogenesis. The EVs released by platelets stimulate the proangiogenic potential of circulating angiogenic cells by increasing their expression of both membrane molecules and soluble factors. Platelet-derived EVs can inhibit angiogenesis by transferring the p22phox and gp91 subunits of NADPH oxidase and increasing the oxidative stress in EC. ? indicates that the exact content of the EVs is not reported; bFGF, basic fibroblast growth factor; EGF, epidermal growth factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; HGF, hepatocyte growth factor; NADPH, nicotinamide adenine dinucleotide phosphate; PI3K, phosphoinositide 3-kinase; RANTES, regulated on activation, normal T-cell–expressed and secreted; ROS, reactive oxygen species; VEGF, vascular endothelial growth factor; and VEGFR, vascular endothelial growth factor receptor. [Powerpoint FIle]

Microvesicles as Cell–Cell Messengers in Cardiovascular Diseases

Microvesicles as Cell–Cell Messengers in Cardiovascular Diseases

Xavier Loyer, Anne-Clémence Vion, Alain Tedgui, Chantal M. Boulanger

Mechanisms involving extracellular vesicles in cell-to-cell communication. Once released, exosomes, microparticles, and apoptotic bodies target recipient cells and are able to transfer information (microRNAs, proteins, etc) by membrane fusion (1), endocytosis (2), or receptor-mediated binding (3). (Illustration credit: Ben Smith). [Powerpoint File]

Circulating MicroRNAs: Novel Biomarkers and Extracellular Communicators in Cardiovascular Disease?

Circulating MicroRNAs: Novel Biomarkers and Extracellular Communicators in Cardiovascular Disease?

Esther E. Creemers, Anke J. Tijsen, Yigal M. Pinto

Cellular release mechanisms and extracellular transportation systems of miRNAs. In the nucleus, miRNAs are transcribed from DNA. A precursor hairpin miRNA (pre-miRNA) is formed after cleavage by the RNase III enzyme Drosha. After being transported into the cytoplasm, the pre-miRNA can be further cleaved into 19- to 23-nucleotide mature miRNA duplexes. One strand of the miRNA duplex can be loaded into the RNA-induced silencing complex (RISC), where it can guide the RISC to specific mRNA targets to prevent translation of the mRNA into protein (1). The other strand may be degraded or released from the cell through export mechanisms described below. In the cytoplasm, pre-miRNAs can also be incorporated into small vesicles called exosomes, which originate from the endosome and are released from cells when multivesicular bodies (MVB) fuse with the plasma membrane (2). Cytoplasmic miRNAs (pre-miRNA or mature miRNA) can also be released by microvesicles, which are released from the cell through blebbing of the plasma membrane (3). miRNAs are also found in circulation in microparticle-free form. These miRNAs can be associated with high-density lipoproteins or bound to RNA-binding proteins such as Ago2. It is not known how these miRNA-protein complexes are released from the cell. These miRNAs may be released passively, as by-products of dead cells, or actively, in an miRNA-specific manner, through interaction with specific membrane channels or proteins (4). Although pre-miRNAs have been detected in exosomes and microvesicles,20 and mature miRNAs have been found in complex with Ago28 and HDL,9 the exact proportion of mature and pre-miRNAs in the different extracellular compartments is not known. Illustration credit: Cosmocyte/Ben Smith. [Powerpoint File]