Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention
| Autor: | Jingjing Cheng, Yunxia Lu, Bing Shen, Qiu Zhang, Li Chen, Guanjun Chen, Li Gui, Chaofei Li |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Nitric Oxide Synthase Type III Endothelium Palmitic Acid Biophysics Diet High-Fat Nitric Oxide Biochemistry Rats Sprague-Dawley Palmitic acid Mice chemistry.chemical_compound Fenofibrate Enos medicine.artery Internal medicine medicine Animals Thoracic aorta Obesity Molecular Biology Aorta Cells Cultured biology Endoplasmic reticulum Endothelial Cells Cell Biology Endoplasmic Reticulum Stress Lipid Metabolism biology.organism_classification Vasodilation medicine.anatomical_structure Endocrinology Gene Expression Regulation chemistry Unfolded protein response Female Endothelium Vascular medicine.drug |
| Zdroj: | Biochemical and Biophysical Research Communications. 458:1-7 |
| ISSN: | 0006-291X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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