title: Oleic acid activates MMPs up-regulation through SIRT1/PPAR-γ inhibition: a probable linkage between obesity and coronary arterial disease.
abstract: 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.
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Chan
authors.affiliation: Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Pei-Ming
authors.initials: PM
authors.lastname: Chu
authors.affiliation: Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chung-Lan
authors.initials: CL
authors.lastname: Kao
authors.affiliation: Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
authors.forename: Yung-Hsin
authors.initials: YH
authors.lastname: Cheng
authors.affiliation: Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan chhung@mail.ncku.edu.tw.
authors.forename: Ching-Hsia
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan kunlingtsai@mail.ncku.edu.tw.
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Tsai
mesh_terms: D002460:Cell Line; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis* / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019301:Oleic Acid / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000096:biosynthesis* / Q000235:genetics; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D047495:PPAR gamma; D019301:Oleic Acid; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Sirtuin 1; coronary arterial disease; matrix metalloproteinases; obesity; smooth muscle cells