Circulating Microparticles

Abstract

Although the presence of subcellular procoagulant particles in highly centrifuged plasma has been known for many years, it was not until 1967 that shed membrane procoagulant fragments from activated platelets were described by Wolf 1 as “platelet dust.” Since then, numerous studies have reported the in vitro release of vesicles from activated or apoptotic cells and their presence in human plasma. Among the different membrane vesicles that cells could release, “microparticles” (MPs) usually refer to those >100 nm in diameter (Figure 1) and derived from the plasma membrane. Smaller vesicles (40 to 100 nm) originating from the endoplasmic membranes are described as “exosomes,” and larger particles (>1.5 μm) containing nuclear material are best known as “apoptotic bodies.”2–4 Both MPs and apoptotic bodies externalize the anionic phospholipid phosphatidylserine, which plays a crucial role in the activation of both coagulation and complement cascades and supports the binding and activity of secreted phospholipase A2. Figure 1. Electron microscopy of circulating MPs from patients with acute coronary syndrome (courtesy of Drs Z. Mallat and M. Wassef). This brief review summarizes the mechanisms leading to the formation and release of MPs, as well as the different approaches to detect their cellular origin in human plasma. This article also discusses the significance of circulating MPs of endothelial origin as both a marker and a trigger of endothelial dysfunction in cardiovascular diseases and the possible prognostic value of plasma MPs to assess cardiovascular risk. The current knowledge on MP formation derives mainly from experiments on isolated or cultured cells showing that both cell activation and cell apoptosis can lead to MP release. However, in vivo mechanisms involved in MP formation and shedding remain mostly unknown. The initial step in MP formation requires plasma membrane budding, leading to the formation of membrane blebs. This step …