Del-etion of Microvesicles From the Circulation

Abstract

Microvesicles (also called microparticles) have become a hot topic recently and transport proteins, mRNA, and microRNA.1–3 They have been proposed to play roles in numerous processes, including coagulation, inflammation, immune response, cell activation, and cancer.1–3 Microvesicles are small (0.1–1 μm) membrane vesicles that are released from activated and apoptotic cells. They contain proteins from their parental cell and are characterized by surface exposure of negatively charged phospholipids, such as phosphatidylserine. Platelets are the primary source of microvesicles in the circulation of healthy individuals, although other cells also release microvesicles. Increased levels of microvesicles are observed in a variety of cardiovascular diseases, including unstable angina, atherosclerosis, and inflammatory vascular diseases. Some microvesicle populations are considered as surrogate biomarkers of vascular disorders and of thrombotic risk.2,3 Article see p 1664 The steady-state level of microvesicles in the circulation reflects a balance between microvesicle generation and clearance. Numerous studies have analyzed the mechanisms of microvesicle formation.1 Stimulation of cells leads to elevated levels of intracellular Ca2+, which results in increased phosphatidylserine on the cell surface, membrane blebbing, and subsequent shedding of microvesicles.1 The importance of phosphatidylserine exposure on platelets and possibly microvesicles in hemostasis is demonstrated by Scott syndrome, a rare bleeding disorder associated with a defect in phosphatidylserine externalization and in microvesicle generation.1 Recently, it was reported that Scott syndrome patients have a mutation in a bidirectional, nonselective Ca2+-dependent channel called TMEM16F.4 In this issue of Circulation , Dasgupta and colleagues5 describe a new pathway of microvesicle clearance from the circulation that involves binding of phosphatidylserine-positive microvesicles to endothelial cells (Figure). Previously, Dasgupta and colleagues6 reported that the major pathway for the removal of microvesicles from the circulation was via binding to splenic …