title: Metformin regulates oxLDL-facilitated endothelial dysfunction by modulation of SIRT1 through repressing LOX-1-modulated oxidative signaling.
abstract: It is suggested that oxLDL is decisive in the initiation and development of atherosclerotic injuries. The up-regulation of oxidative stress and the generation of ROS act as key modulators in developing pro-atherosclerotic and anti-atherosclerotic processes in the human endothelial wall. In this present study, we confirmed that metformin enhanced SIRT1 and AMPK expression in human umbilical vein endothelial cells (HUVECs). Metformin also inhibited oxLDL-increased LOX-1 expression and oxLDL-collapsed AKT/eNOS levels. However, silencing SIRT1 and AMPK diminished the protective function of metformin against oxidative injuries. These results provide a new insight regarding the possible molecular mechanisms of metformin.
authors.affiliation: Department of Physical Therapy, College of Medicine, National Cheng Kung University,Tainan, Taiwan.|Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ching-Hsia
authors.initials: CH
authors.lastname: Hung
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: Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Department of Physical Therapy, Shu-Zen Junior College of Medicine and Management, Taiwan.
authors.forename: Huei-Chen
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Department of Physical Therapy, College of Medicine, National Cheng Kung University,Tainan, Taiwan.
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Tsai
mesh_terms: D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008687:Metformin / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C099252:oxidized low density lipoprotein; D008687:Metformin; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Gerotarget; SIRT1; endothelial dysfunction; metformin; oxLDL