Microparticles and cardiovascular diseases

Abstract

Microparticles are a distinctive group of small vesicles, without nucleus, which are involved as significant modulators in several physiological and pathophysiological mechanisms. Plasma microparticles from various cellular lines have been subject of research. Data suggest that they are key players in development and manifestation of cardiovascular diseases and their presence, in high levels, is associated with chronic inflammation, endothelial damage and thrombosis. The strong correlation of microparticle levels with several outcomes in cardiovascular diseases has led to their utilization as biomarkers. Despite the limited clinical application at present, their significance emerges, mainly because their detection and enumeration methods are improving. This review article summarizes the evidence derived from research, related with the genesis and the function of microparticles in the presence of various cardiovascular risk factors and conditions. The current data provide a substrate for several theories of how microparticles influence various cellular mechanisms by transferring biological information.

Keywords: Microparticles; atherosclerosis; cardiovascular; heart failure; inflammation; thrombosis.

Figure 1.

Extracellular vesicles. (1): Production of microparticles after stimulation of paternal cell. Microparticles are released from activated cell after outwards rearrangement of the cellular membrane. (2): Production of microparticles during apoptotic process. Microparticles are released before the formation of apoptotic bodies. (3): Endosomes in multivesicular body. After exocytosis of the endosomes into the extracellular environment may be called exosomes.

Figure 2.

Mechanisms involved in the generation of the microparticles. (1): After activation of the cell an increased Ca⁺² influx follows. (2): Externalisation of phosphatidylserine mediated by ATP-dependent floppases, scramblases and membrane pores. (3): Cytoskeleton Protein reconfiguration in order to produce outward membrane blebs. Capsases, caplains and Rho kinases are involved in the process.

Figure 3.

Microparticle content. External surface of plasma membrane in general contains negatively charged phosphatidylserine along with membrane proteins like major histocompatibility complex molecules, integrins and tissue factor. In the cytosol, there is no organised nucleus but apart from cytoskeleton proteins and enzymes, nucleic acid remnants (DNA or RNA) are present.

Figure 4.

Mechanisms and molecules related with Microparticle induced coagulation. Abbreviations: PS: phospatildylserine; GLA: γ-carboxyglutamic acid; clotting proteins factors VII, IX, X and prothrombin. Negatively charged PS electrostatically attract the positively charged segment of clotting proteins/GLA complex and induce thrombogenesis. Tissue factor may also activate the coagulation cascade via the FVII/VIIa complex. Additionally, inhibition of fibrinolysis by microparticle membrane proteins such as plasminogen activator inhibitor-1 and protein S may augment thrombogenesis.

Figure 5.

Mechanisms associated with initiation and progression of atherosclerosis mediated by Microparticles (MPs).

Figure 6.

Cardiovascular diseases and microparticles. Flow chart which summarises the role of microparticles in the genesis (related with several risk factors) and manifestation of cardiovascular diseases. Utilisation as biomarkers to assess disease activity/severity, prognosis and treatment guidance is emerging as detection and enumeration methods for microparticles are improving.