The Impact of Vascular Disease Treatment on Platelet-Derived Microvesicles

Abstract

Platelet-derived microvesicles (pMVs) are small, heterogeneous vesicles released from platelet membranes as a result of activation. These microvesicles possess a wide range of properties, including prothrombotic, proatherogenic, proinflammatory, immunomodulatory, and even anticoagulant activity. The elevated release of these microvesicles has been observed in various metabolic, inflammatory, thrombotic, and vascular diseases, including ischemic heart disease, stroke, hypertension, diabetes, and connective tissue disease. Modulation of both pMV generation and the expression of their surface molecules may have beneficial clinical implications and could become a novel therapeutic target. However, mechanisms by which pharmacological agents can modify pMV formation are elusive. The purpose of this review is to discuss the effects of drugs routinely used in primary and secondary prevention of vascular disease on the release of pMV and expression of their surface procoagulant and proinflammatory molecules.

Keywords: Antiplatelet therapy; Cardiovascular disease; Cerebrovascular disease; Platelet-derived microparticles; Platelet-derived microvesicles (pMV); Statins.

Fig. 1

Potential effects of vascular disease treatment on pMV release. Increase in intraplatelet calcium concentration is the principal step in pMV formation. ADP receptor inhibitors increase the intraplatelet concentration of cAMP thereby decreasing platelet vesiculation. GP IIb-IIIa antagonists inhibit binding of fibrinogen thereby preventing the second wave of platelet activation. Statins inhibit platelet vesiculation multi-directional—reducing NF-κB activity and increasing exposure of PPARs and via the ROCK pathway. Fibrates as PPAR agonists increase the levels of both cAMP and cGMP and decrease calcium concentration. Calcium channel blockers inhibit calcium influx and decrease intracellular calcium concentration. Platelet-derived microvesicles transfer AA between platelets and ECs. Microvesicles also metabolize AA to TXA2. AA arachidonic acid, ADP adenosine diphosphate, ASA acetylsalicylic acid, COX cyclooxygenase, GP glycoprotein, MLCP myosin light chain phosphatise, MAPK mitogen-activated protein kinase, NF-κB nuclear factor kappa B, PDE phosphodiestherase, PGH2 prostaglandin H2, PKC protein kinase C, PLA2 phospholipase A2, PLT platelet, p38MAPK mitogen-activated protein kinase p38, pMV platelet-derived microvesicles, PPAR peroxisome proliferator-activated receptor, PS phosphatidylserine, PUFAs polyunsaturated fatty acids, ROCK Rho-associated protein kinase, TNF-α tumor necrosis factor α, TXA2 thromboxane A2, TXA2R thromboxane A2 receptor