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Changes in the Levels of Adiponectin and MCP‐1 may be Responsible for Cigarette Smoke‐Induced Atherosclerosis
Author(s) -
Yuan H.,
Wong L.,
Bhattacharya M.,
Ma C.,
Sielaff R.,
Zafarani M.,
MartinsGreen M.
Publication year - 2008
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2005.130216bi.x
Subject(s) - adiponectin , fatty streak , chemistry , foam cell , blood vessel , cigarette smoke , vasa vasorum , medicine , macrophage , microbiology and biotechnology , biology , in vitro , biochemistry , aorta , obesity , insulin resistance , environmental health
Atherosclerotic plaque formation involves recruitment and adhesion of circulating monocytes to sites of blood vessel wall injury followed by their migration into the subendothelial space stimulated by MCP‐1 (monocyte‐chemoattractant‐protein1). Monocytes differentiate into macrophages, cells that release a variety of factors and take up oxidized LDL, becoming foam cells. Smooth muscle cells of the vessel wall differentiate and migrate to the subendothelial space, interact with foam cells and components of the ECM to form a “fatty streak,” the precursor of plaque. Adiponectin, a protein secreted by adipocytes, circulates in the blood, maintains blood vessel wall stability and inhibits foam cell formation. Cigarette smoke is a major risk factor of atherosclerosis, although the mechanisms remain unknown. We showed previously that both firsthand and secondhand cigarette smoke stimulate MCP‐1 in endothelial cells and others have shown that adiponectin levels in smokers with cardiovascular disease are reduced. We hypothesized that a localized increase in MCP‐1 and a decrease in adiponectin are critical for cigarette smoke‐induced plaque formation. To test this possibility, we used mice transgenic for human ApoB100, a model system that closely mimics human conditions that lead to atherosclerosis, and a smoking machine that closely simulates human smoking. We found that, in smoking mice, the micro vessels in the heart tissue are often filled with lipids, the areas surrounding the plaque‐prone regions have numerous neutrophils, that these cells express high levels of MCP‐1, and that the plaques are larger than in control mice. In addition, the level of the adiponectin monomer in the blood of smoking mice is lower and the presence of this protein in the heart tissue is also decreased. In conclusion, the decrease in adiponectin and the increase in MCP‐1 levels may be responsible for cigarette smoke‐induced atherogenesis.