Oleic acid activates MMPs up-regulation through SIRT1/PPAR-γ inhibition: a probable linkage between obesity and coronary arterial disease.

Obesity is positively related to the growing prevalence of coronary arterial disease (CAD). It is well established in terms of the plasma concentrations of free fatty acid (FFA) that are up-regulated in cases associating with obesity. Oleic acid (OA) is known as the most abundant monounsaturated fatty acid in the human circulatory system. Several pro-atherosclerotic responses of OA have been established. Sirtuin 1 (SIRT1) acts as a key role in regulating the normal physical function in smooth muscle cells (SMCs). SIRT1 activation is developed as a novel approach to delay the progression of atherosclerotic injuries. However, the mechanism is still unclear as to whether OA affects SIRT1 expression and its activity in SMCs. We confirmed that OA treatment represses SIRT1 and peroxisome proliferator-activated receptors-γ levels in SMCs. Moreover, OA enhances by transforming the growth factor-β1 (TGF-β1) release via activation of NF-κB. OA causes NO production by inducing the inducible nitric oxide synthase overexpression, thereby promoting the secretions of matrix metalloproteinases-1 (MMP-1) and MMP-3. Overall, we suggested that OA enhances MMPs activation through SIRT1 down-regulation. Therefore, our findings might provide a novel route for developing new therapeutic treatments for FFAs-related CADs.