Endothelial microparticles in diseases.
Microparticles are submicron vesicles shed from plasma membranes in response to cell activation, injury, and/or apoptosis. The measurement of the phospholipid content (mainly phosphatidylserine; PSer) of microparticles and the detection of proteins specific for the cells from which they are derived has allowed their quantification and characterization. Microparticles of various cellular origin (platelets, leukocytes, endothelial cells) are found in the plasma of healthy subjects, and their amount increases under pathological conditions. Endothelial microparticles (EMP) not only constitute an emerging marker of endothelial dysfunction, but are also considered to play a major biological role in inflammation, vascular injury, angiogenesis, and thrombosis. Although the mechanisms leading to their in vivo formation remain obscure, the release of EMP from cultured cells can be caused in vitro by a number of cytokines and apoptotic stimuli. Recent studies indicate that EMP are able to decrease nitric-oxide-dependent vasodilation, increase arterial stiffness, promote inflammation, and initiate thrombosis at their PSer-rich membrane, which highly co-expresses tissue factor. EMP are known to be elevated in acute coronary syndromes, in severe hypertension with end organ damage, and in thrombotic thrombocytopenic purpura, all conditions associated with endothelial injury and pro-thrombotic state. The release of EMP has also been associated with endothelial dysfunction of patients with multiple sclerosis and lupus anticoagulant. More recent studies have focused on the role of low shear stress leading to endothelial cell apoptosis and subsequent EMP release in end-stage renal disease. Improved knowledge of EMP composition, their biological effects, and the mechanisms leading to their clearance will probably open new therapeutic approaches in the treatment of atherothrombosis.
Chironi
Gilles N
GN
AP-HP, Hôpital Européen Georges Pompidou, Centre de Médecine Préventive Cardiovasculaire and Université René Descartes, Paris, France. gilles.chironi@brs.aphp.fr
Boulanger
Chantal M
CM
Simon
Alain
A
Dignat-George
Françoise
F
Freyssinet
Jean-Marie
JM
Tedgui
Alain
A
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001808:Blood Vessels / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D002318:Cardiovascular Diseases / Q000097:blood* / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000473:pathology; D016682:Lupus Coagulation Inhibitor / Q000097:blood; D009103:Multiple Sclerosis / Q000097:blood* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000097:blood* / Q000473:pathology; D009569:Nitric Oxide / Q000097:blood; D010718:Phosphatidylserines; D033081:Shear Strength; D013925:Thromboplastin / Q000378:metabolism
D015415:Biomarkers; D016207:Cytokines; D016682:Lupus Coagulation Inhibitor; D010718:Phosphatidylserines; D009569:Nitric Oxide; D013925:Thromboplastin