Shed membrane microparticles from circulating and vascular cells in regulating vascular function

Abstract

Inflammation has a pivotal role in the development of atherosclerosis and acute activation of the vascular wall with consecutive local thrombosis and altered vasomotion. This process is orchestrated by the interactions between inflammatory cells, such as platelets and T and B lymphocytes, and vascular cells, endothelial cells, and smooth muscle cells. When they are activated by an agonist, shear stress, or apoptosis, these cells release vesicles shed from the blebbing plasma membrane called microparticles. Microparticles harbor cell surface proteins and contain cytoplasmic components of the original cell. They exhibit negatively charged phospholipids, chiefly phosphatidylserine, at their surface, which accounts for their procoagulant character and proinflammatory properties, including alteration of vascular function. Elevated levels of circulating microparticles have been detected in pathological states associated with vascular dysfunction, including attenuation of endothelium-dependent vasodilatation and/or alteration of responsiveness of vascular smooth muscle to vasoconstrictor stimuli in conductance and resistance arteries. This review points out the characteristics of microparticles as well as the biological messages they can mediate. In particular, it summarizes the signaling cascades involved in microparticle-induced vascular dysfunction with special attention to the cellular origin of these vesicles (platelet, endothelial, and leukocytic), which may explain their differential consequences on vascular remodeling. The available information provides a rationale for the paracrine role of microparticles as vectors of transcellular exchange of message between circulating cells and cells from the vascular wall.

Platelet Mediated Complement Activation

“…Compared to activated platelets, PMP can express 50-100 fold higher procoagulant activity (Sinauridze, Kireev, Popenko, Pichugin, Panteleev, Krymskaya, and Ataullakhanov 2007). They retain selected platelet membrane constituents, including glycoproteins Ib, IIbIIIa, and P-selectin (Gawaz, Ott, Reininger, Heinzmann, Neumann 1996;George, Pickett, Saucerman, McEver, Kunicki, Kieffer, and Newman 1986) which support vascular inflammation by participating in heterotypic communication with leukocytes and vascular endothelial cells (Martinez, Tesse, Zobairi, and Andriantsitohaina 2005;Barry, Pratico, Savani, and FitzGerald 1998).…”

Circulating Microparticles

“…63 In addition, impaired vascular reactivity because of increased expression of inducible NO synthase and cyclooxygenase-2 (COX2) in smooth muscle cells has been observed in the isolated mouse aorta after exposure to MPs derived from a T-cell line or from circulating MPs isolated from the plasma of diabetic patients. 60 Further details on the molecular mechanisms of MP effects on vascular reactivity can be found in Martinez et al 64 Finally, endothelial, platelet, and tumor cell-derived MPs seem to be able to stimulate angiogenesis, an effect mediated by reactive oxygen species, metalloproteinases, growth factors such as vascular endothelial growth factor, or sphingomyelin. [65][66][67][68][69] Apoptotic bodies from endothelial cells (larger than MPs) could also contribute to tissue repair mechanisms by stimulating the differentiation of progenitor cells.…”

Phosphatidylinositol 3-Kinase and Xanthine Oxidase Regulate Nitric Oxide and Reactive Oxygen Species Productions by Apoptotic Lymphocyte Microparticles in Endothelial Cells

“…MPs constitute a heterogeneous population, differing in cellular origin, number, size, antigenic composition, and functional properties (3). MPs bear cell surface proteins and the cytoplasmic component of the original cell and exhibit negatively charged phospholipids such as phosphatidylserine, and tissue factor (3,4), accounting for their procoagulant character and proinflammatory properties, including alteration of vascular function (3,4).…”

“…MPs bear cell surface proteins and the cytoplasmic component of the original cell and exhibit negatively charged phospholipids such as phosphatidylserine, and tissue factor (3,4), accounting for their procoagulant character and proinflammatory properties, including alteration of vascular function (3,4). MPs may transfer bioactive molecules to other cells, different than those from which they have been produced, thereby stimulating cells to produce cytokines, cell adhesion molecules, growth factors and tissue factor, and modulate endothelial functions (3). However, the mechanisms involved in the effects produced by MPs are not fully elucidated.…”