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Saturated fatty acid, palmitate, promotes smooth muscle phenotypic modulation and exacerbates neointima formation.
Author(s) -
Shen Hua,
Manabe Ichiro,
Eguchi Kosei,
Fujiu Katsuhito,
Nagai Ryozo
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.357.3
Subject(s) - neointima , nox1 , medicine , endocrinology , gene knockdown , nadph oxidase , chemistry , microbiology and biotechnology , oxidative stress , biology , biochemistry , gene , restenosis , stent
Metabolic syndrome is a major risk factor for atherosclerotic cardiovascular disease. Circulating free fatty acid (FFA) levels are known to be increased in obese individuals.Increased levels of FFAs have been shown to be associated with higher risks for cardiovascular disease. However, little is known regarding effects of FFAs on vascular cells.We found that palmitate, the major circulating free fatty acid, induced expression of KLF5 and inflammatory genes, such as MMPs, and elicited smooth muscle cell (SMC) phenotypic modulation. When palmitate was administered to the mice whose carotid arteries were ligated, palmitate dramatically exacerbated neointima formation. Palmitate induced ROS formation, partly by induction of NADPH oxidase, NOX1 in cultured SMCs. NOX1 expression levels were also induced by palmitate infusion in mouse aortas and carotid arteries in vivo. Inhibition of NOX1 attenuated palmitate‐induced phenotypic modulation. Furthermore, we found that toll‐like receptor (TLR) signaling mediated the response to palmitate. Knockdown of Myd88, adaptor protein for TLRs, significantly reduced NOX1 induction and ROS formation. Taken together, palmitate promotes neointima formation via TLR‐signaling mediated ROS production and inflammatory gene expression. Palmitate appears to be a key common obesity‐related factor involved in pathogenesis of both cardiovascular and metabolic diseases.