Circulating Microparticles as Therapeutic Targets in Cardiovascular Diseases

Abstract

Microparticles are a heterogeneous population of small membrane-coated vesicles released by several cell lines upon activation or apoptosis. Microparticle generation seems to be a well regulated process, although these vesicles are highly variable in size, composition and function. Despite being previously considered inert debris without specific function, recent data demonstrated important pathophysiologic mechanisms orchestrated by microparticles in vascular diseases associated with endothelial dysfunction. These vesicles have been implicated, among others, in the pathogenesis of thrombosis, diabetes, inflammation, atherosclerosis and vascular cell proliferation. In addition to microparticles, circulating activated cells release smaller vesicles denominated exosomes that can also participate in vascular derangement. This mechanistic role of microparticles and exosomes in mediating vascular dysfunction indicates that they may represent novel pathways in short or long-distance paracrine transcellular signaling in vascular environment. The most recent patents regarding microparticles and exosomes are related to their procoagulant potential (U.S. Pat. No. 7005271), role in immune activation of T or B cells (Eurasian Pat. No. 0002827B1) and role in peptide vaccination (World Pat. No. 9705900A1). These commercial applications of microvesicles will be discussed in this review, as well as mechanisms involved in their origin, composition and participation in the pathogenesis of cardiovascular diseases.

Essential role of Notch signaling in apoptosis of human pancreatic tumoral cells mediated by exosomal nanoparticles

“…9 However, the presence of these vesicles in human blood suggests that they have a physiological role in cellcell or organ-organ communication. 10 Exosomes are believed to play an antitumoral role through immune cells. 8 We recently showed that human pancreatic tumoral cells expressed exosomal nanoparticles that are rich in lipid-forming microdomains termed rafts.…”

Cellular Mechanisms Underlying the Formation of Circulating Microparticles

“…[15][16][17] These observations suggest that MPs can be viewed as a major therapeutic target, not only in the inhibition of arterial and venous thrombosis but also in the containment of the systemic inflammatory response and atherosclerosis. 18 In this report, we review the cellular mechanisms governing the formation and the dynamics of circulating MPs. The significance of MPs as potential therapeutic and diagnostic targets for a number of atherothrombotic diseases with unmet medical needs will be discussed.…”

The Role of Smoothened and Hh Signaling in Neovascularization

“…Particular attention had been paid to this novel method of cell communication, because extracellular vesicles are able to exchange biological message between different kinds of cells, not only in the proximity area of their generation but also far from cells they stem from. Hemostasis and thrombosis, diabetes, inflammation, atherosclerosis, angiogenesis, tumor progression, apoptosis, vascular cell proliferation, and outgrowth of transplanted hematopoietic stem cells [156][157][158] represent some physiological and pathological situations where generation of extracellular vesicles is enhanced and subsequently may be involved in altered angiogenesis. In fact, it has been shown that different stages of vessel formation are regulated by extracellular vesicles.…”