Atherothrombosis: Plaque instability and thrombogenesis☆,☆☆
Section snippets
Normal endothelial function
Normal endothelial function involves the expression of a host of surface proteins and secreted substances that maintain both vascular tone as well as a nonthrombogenic milieu. This local environment results, in part, from the physical barrier provided by an intact endothelial cell (EC) monolayer that protects circulating blood from exposure to prothrombotic subendothelial matrix proteins. An intact endothelium affords a smooth laminar surface that facilitates blood flow. The endothelium also
Plaque development, destabilization, and thrombosis
Atherosclerosis can be regarded as a chronic inflammatory process during which monocytes and lymphocytes migrate into the subintimal space of the arterial wall. Progressive expansion of this lesion, owing partly to lipid accumulation, leads to luminal narrowing and a reduction in blood flow. A fibrous cap composed of matrix proteins and smooth muscle cells characterizes the surface of the developing atherosclerotic lesion. Disruption of this fibrous cap (destabilization) promotes thrombosis
Future directions
The ability of clinicians to recognize an ACS and differentiate it from other noncardiac causes of chest pain syndromes remains a formidable challenge in the treatment of cardiovascular disease. As atherothrombosis is a form of chronic inflammation with plaque rupture and thrombosis in the setting of a superimposed acute inflammatory process, it follows that markers of acute inflammation may be indicators of an underlying unstable plaque phenotype. Indeed, although recent work has demonstrated
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Supported in part by NIH grants HL55993, HL58976, HL61795, and HL04399.
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Address reprint requests to Joseph Loscalzo, MD, 715 Albany St., W-507, Boston, MA 02118-2526.