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Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture (2005)
| Citations: | 5 - 0 self |
BibTeX
@MISC{Boyle05macrophageactivation,
author = {J. J. Boyle},
title = {Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture},
year = {2005}
}
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Abstract
Abstract: Atherosclerosis is still an important disease. It accounts for 39 % of deaths in the U.K. and 12 million U.S citizens have atherosclerosis-associated disease. Atherosclerosis may exert clinical effects by slow narrowing, producing stable angina or dramatic rupture, producing acute coronary syndromes such as unstable angina or myocardial infarction and death. Macrophages are abundant in ruptured atherosclerotic plaques. Macrophages are innate immune effectors, i.e. they are activated without antigenic specificity. This may make them liable to indiscriminate tissue damage, since they are less selective than lymphocytes. Macrophages are recruited and activated by many signals and have an impressive armamentarium of molecules to promote tissue damage. Macrophage recruitment by abnormal endothelium over developing atherosclerotic plaques, is aided by endothelial expression of adhesion molecules (ICAM-1, VCAM, ELAM). Use of knockout mice has implicated the chemoattractant cytokine (chemokine) MCP-1 in attracting macrophage recruitment in atherosclerosis. Macrophage-activation stimuli associated with atherosclerotic risk factors include oxidised low density lipoprotein (oxLDL, ‘bad cholesterol’), advanced glycosylation end products (AGEs) of diabetes, angiotensin II and endothelin. Substantial work has clarified macrophage activation by OxLDL via macrophage scavenger receptors (MSRs), especially MSRA and CD36. Activated macrophages express effector molecules that kill cells and degrade extracellular matrix. These include Fas-L and nitric oxide (NO). Macrophage NO is derived from the high output inducible nitric oxide synthase (iNOS) pathway and upregulates vascular smooth muscle (VSMC) cell surface Fas,
Keyphrases
macrophage activation plaque rupture tissue damage macrophage recruitment many signal atherosclerotic plaque adhesion molecule bad cholesterol low density lipoprotein slow narrowing cell surface fa chemoattractant cytokine ruptured atherosclerotic plaque vascular smooth muscle antigenic specificity abnormal endothelium extracellular matrix angiotensin ii unstable angina knockout mouse endothelial expression macrophage-activation stimulus innate immune effector stable angina important disease clinical effect dramatic rupture atherosclerotic risk factor atherosclerosis-associated disease nitric oxide macrophage scavenger receptor substantial work glycosylation end product acute coronary syndrome impressive armamentarium myocardial infarction express effector molecule u.s citizen
