These results demonstrate that microparticles are more abundant and more thrombogenic in human atherosclerotic plaques than in plasma. The different cellular origins of plaque and plasma microparticles might explain the increased thrombogenic activity of plaque microparticles.

Blood vessels are permanently subjected to mechanical forces in the form of stretch, encompassing cyclic mechanical strain due to the pulsatile nature of blood flow and shear stress. Significant variations in mechanical forces, of physiological or physiopathological nature, occur in vivo. These are accompanied by phenotypical modulation of smooth muscle cells and endothelial cells, producing structural modifications of the arterial wall. In all the cases, vascular remodelling can be allotted to a modification of the tensional strain or shear, and underlie a trend to reestablish baseline mechanical conditions. Vascular cells are equipped with numerous receptors that allow them to detect and respond to the mechanical forces generated by pressure and shear stress. The cytoskeleton and other structural components have an established role in mechanotransduction, being able to transmit and modulate tension within the cell via focal adhesion sites, integrins, cellular junctions and the extracellular matrix. Mechanical forces also initiate complex signal transduction cascades, including nuclear factor-jB and mitogen-activated protein kinase pathways, leading to functional changes within the cell.

Rationale and Objective: Membrane-shed submicron microparticles (MPs) released following cell activation or apoptosis accumulate in atherosclerotic plaques, where they stimulate endothelial proliferation and neovessel formation. The aim of the study was to assess whether or not MPs isolated from human atherosclerotic plaques contribute to increased endothelial adhesion molecules expression and monocyte recruitment. Method and Results:Human umbilical vein and coronary artery endothelial cells were exposed to MPs isolated from endarterectomy specimens (n‫)26؍‬ and characterized by externalized phosphatidylserine. Endothelial exposure to plaque, but not circulating, MPs increased ICAM-1 levels in a concentration-dependant manner (3.4-fold increase) without affecting ICAM-1 mRNA levels. Plaque MPs harbored ICAM-1 and transferred this adhesion molecule to endothelial cell membrane in a phosphatidylserine-dependent manner. MP-borne ICAM-1 was functionally integrated into cell membrane as demonstrated by the increased ERK1/2 phosphorylation following ICAM-1 ligation. Plaque MPs stimulated endothelial monocyte adhesion both in culture and in isolated perfused mouse carotid. This effect was also observed under flow condition and was prevented by anti-LFA-1 and anti-ICAM-1 neutralizing antibodies. MPs isolated from symptomatic plaques were more potent in stimulating monocyte adhesion than MPs from asymptomatic patients. Plaque MPs did not affect the release of interleukin-6, interleukin-8, or MCP-1, nor the expression of VCAM-1 and E-selectin. Key Words: microparticle Ⅲ ICAM-1 Ⅲ adhesion Ⅲ monocyte Ⅲ microvesicle A therosclerosis is a chronic inflammatory disease characterized by the accumulation of leukocytes, lipids, and fibrous tissue in the intima of arteries. 1 In atherosclerotic plaques, endothelial cells express elevated amounts of adhesion molecules such as selectins (P-selectin and E-selectin) and intercellular (ICAM-1) and vascular (VCAM-1) adhesion molecules at their surface. 1,2 Cytokines and chemokines are also secreted in excess by activated vascular cells in this context. These conditions favor the recruitment and the accumulation of monocytes and lymphocytes in the intima of vessels. 1,2 Human atherosclerotic plaques contain large amounts of microparticles (MPs), which are submicron membrane vesicles released following cell activation or apoptosis. [3][4][5] MPs harbor at their surface most of the membrane-associated proteins of the cells they stem from and are characterized by the loss of plasma membrane asymmetry resulting in the exposure of phosphatidylserine on their outer leaflet. 6,7 MPs isolated from human atherosclerotic lesions are highly thrombogenic and originate from multiple cells, including macrophages, lymphocytes, erythrocytes, and smooth muscle and endothelial cells. 4,5 MPs are no longer taken as innocent bystanders because several studies point out that MPs generated in vitro from cultured cells can affect several cellular functions, including inflammatory responses. 8 -15 However,...