title: Eicosapentaenoic acid protects against palmitic acid-induced endothelial dysfunction via activation of the AMPK/eNOS pathway.
abstract: Recent studies have shown that free fatty acids are associated with chronic inflammation, which may be involved in vascular injury. The intake of eicosapentaenoic acid (EPA) can decrease cardiovascular disease risks, but the protective mechanisms of EPA on endothelial cells remain unclear. In this study, primary human umbilical vein endothelial cells (HUVECs) treated with palmitic acid (PA) were used to explore the protective effects of EPA. The results revealed that EPA attenuated PA-induced cell death and activation of apoptosis-related proteins, such as caspase-3, p53 and Bax. Additionally, EPA reduced the PA-induced increase in the generation of reactive oxygen species, the activation of NADPH oxidase, and the upregulation of inducible nitric oxide synthase (iNOS). EPA also restored the PA-mediated reduction of endothelial nitric oxide synthase (eNOS) and AMP-activated protein kinase (AMPK) phosphorylation. Using AMPK siRNA and the specific inhibitor compound C, we found that EPA restored the PA-mediated inhibitions of eNOS and AKT activities via activation of AMPK. Furthermore, the NF-κB signals that are mediated by p38 mitogen-activated protein kinase (MAPK) were involved in protective effects of EPA. In summary, these results provide new insight into the possible molecular mechanisms by which EPA protects against atherogenesis via the AMPK/eNOS-related pathway.
authors.affiliation: Department of Microbiology, School of Medicine, China Medical University, 40402 Taichung, Taiwan. chlee@mail.cmu.edu.tw.
authors.forename: Che-Hsin
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, 40402 Taichung, Taiwan. miracle0820@gmail.com.
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
authors.affiliation: Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, 40402 Taichung, Taiwan. ouhc@mail.cmu.edu.tw.
authors.forename: Hsiu-Chung
authors.initials: HC
authors.lastname: Ou
authors.affiliation: Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, 40402 Taichung, Taiwan. miracle0820@gmail.com.
authors.forename: Su-Chuan
authors.initials: SC
authors.lastname: Lai
authors.affiliation: Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, 40402 Taichung, Taiwan. chengyu@mailcmu.edu.tw.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Cheng
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D020536:Enzyme Activators / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D019308:Palmitic Acid / Q000633:toxicity; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D020536:Enzyme Activators; D016328:NF-kappa B; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D019308:Palmitic Acid; D015118:Eicosapentaenoic Acid; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D053148:Caspase 3