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8TH INTERNATIONAL SYMPOSIUM ON RESISTANCE ARTERIES
New Developments in Resistance Artery Research: From Molecular Biology to Bedside
1Institut d'Hématologie et d'Immunologie, Unité 143, Institut National de la Santé et de la Recherche Médicale, Université Louis Pasteur, Strasbourg; and 2Pharmacologie des Interactions Cellulaires et Moléculaires, UMR Centre National de la Recherche Scientifique 7034, Université Louis Pasteur, Illkirch, France
Submitted 19 August 2004 ; accepted in final form 23 September 2004
Inflammation has a pivotal role in the development of atherosclerosis and acute activation of the vascular wall with consecutive local thrombosis and altered vasomotion. This process is orchestrated by the interactions between inflammatory cells, such as platelets and T and B lymphocytes, and vascular cells, endothelial cells, and smooth muscle cells. When they are activated by an agonist, shear stress, or apoptosis, these cells release vesicles shed from the blebbing plasma membrane called microparticles. Microparticles harbor cell surface proteins and contain cytoplasmic components of the original cell. They exhibit negatively charged phospholipids, chiefly phosphatidylserine, at their surface, which accounts for their procoagulant character and proinflammatory properties, including alteration of vascular function. Elevated levels of circulating microparticles have been detected in pathological states associated with vascular dysfunction, including attenuation of endothelium-dependent vasodilatation and/or alteration of responsiveness of vascular smooth muscle to vasoconstrictor stimuli in conductance and resistance arteries. This review points out the characteristics of microparticles as well as the biological messages they can mediate. In particular, it summarizes the signaling cascades involved in microparticle-induced vascular dysfunction with special attention to the cellular origin of these vesicles (platelet, endothelial, and leukocytic), which may explain their differential consequences on vascular remodeling. The available information provides a rationale for the paracrine role of microparticles as vectors of transcellular exchange of message between circulating cells and cells from the vascular wall.
microvesicles; nitric oxide synthase; cyclooxygenase; inflammation; vascular diseases
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