title: Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention.
abstract: Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but whether its protective effect on endothelium-dependent vasodilatation (EDV) in thoracic aorta is related with endoplasmic reticulum (ER) stress remains unknown. In this study, female Sprauge Dawley rats were divided into standard chow diets (SCD), high-fat diets (HFD) and HFD plus FF treatment group (HFD + FF) randomly. The rats of latter two groups were given HFD feeding for 5 months, then HFD + FF rats were treated with FF (30 mg/kg, once daily) via gavage for another 2 months. The pathological and tensional changes, protein expression of eNOS, and ER stress related genes in thoracic aorta were measured. Then impacts of palmitic acid (PA) and FF on EDV of thoracic aorta from normal female SD rats were observed. Ultimately the expression of ER stress related genes were assessed in primary mouse aortic endothelial cells (MAEC) treated by fenofibric acid (FA) and PA. We found that FF treatment improved serum lipid levels and pathological changes in thoracic aorta, accompanied with decreased ER stress and increased phosphorylation of eNOS. FF pretreatment also improved EDV impaired by different concentrations of PA treatment. The dose- and time-dependent inhibition of cell proliferation by PA were inverted by FA pretreatment. Phosphorylation of eNOS and expression of ER stress related genes were all inverted by FA pretreatment in PA-treated MAEC. Our findings show that fenofibrate recovers damaged EDV by chronic HFD feeding and acute stimulation of PA, this effect is related with decreased ER stress and increased phosphorylation of eNOS.
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032, PR China; The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032, PR China. Electronic address: wwwdluyx@sina.com.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032, PR China; Department of Medical Laboratory, Anhui Provincial Hospital, Hefei, Anhui 230001, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Chaofei
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Chen
authors.affiliation: The Comprehensive Laboratory, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Gui
authors.affiliation: Department of Physiology, Anhui Medical University, Hefei, Anhui 230032, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, PR China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D059305:Diet, High-Fat / Q000009:adverse effects*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D011345:Fenofibrate / Q000031:analogs & derivatives / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy; D019308:Palmitic Acid / Q000009:adverse effects*; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
chemical_list: D019308:Palmitic Acid; D009569:Nitric Oxide; C006012:fenofibric acid; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D011345:Fenofibrate
keywords: Endoplasmic reticulum stress; Endothelial nitric oxide synthase; Endothelium-dependent vasodilatation; Fenofibrate; High-fat diet; Palmitic acid