Protective effect of atorvastatin meditated by HMGCR gene on diabetic rats with atherosclerosis: An in vivo and in vitro study - 11/06/18
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| pages | 12 |
| Iconographies | 9 |
| Vidéos | 0 |
| Autres | 0 |
Graphical abstract |
AVT treatment and upregulation of HMGCR can improve diabetic atherosclerosis lesion by decreasing lipid content, repairing endothelial function and reducing thrombosis. What’s more, overexpression of HMGCR together with AVT intervention is the most effective way to improve diabetic atherosclerosis lesion.
Highlights |
• | To investigate the effect of atorvastatin and HMGCR on diabetic atherosclerosis. |
• | Atorvastatin can attenuate histopathological changes in diabetic atherosclerosis. |
• | Overexpressed HMGCR promotes LDLR, suppresses FASN and cell apoptosis. |
• | Silenced HMGCR reverses protection of atorvastatin on diabetic atherosclerosis. |
• | Overexpressed HMGCR with atorvastatin best protects diabetic atherosclerosis. |
Abstract |
Background |
Accelerated atherosclerosis in patients suffering from diabetes represents a major cause of morbidity and mortality. The aim of present study was to investigate the protective effects conferred by atorvastatin (AVT) meditated by the HMGCR gene in diabetic rats with atherosclerosis.
Methods |
Serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), fasting blood glucose (FBG) and serum insulin (INS) were all determined by means of in vivo experiments. Following the establishment of the diabetic model of atherosclerosis, the expressions of HMGCR, low density lipoprotein receptor (LDLR), fatty acid synthase (FASN) were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis in the vitro experiments. Flow cytometry was adopted in order to detect cell cycle and apoptosis.
Results |
The in vivo experiments results indicated that FBG and INS among the diabetic arteriosclerosis rats exhibited markedly higher levels; after injected with AVT and HMGCR, decreased contents of TC, TG, LDL-C and VLDL-C, while increased contents of HDL-C as well as an increased positive rate of HMGCR protein expression were observed. In vitro experiment, the mRNA and protein expression of LDLR were increased and FASN were decreased in cells transfected with HMGCR and AVT; with a greater number of cells arrested at the S phase and less in the G0/G1 phase, as well as data indicating the rate of apoptosis was inhibited after HMGCR and AVT transfection processes.
Conclusion |
The key findings of the present study suggested that the protective effect conferred by AVT in diabetic rats with atherosclerosis was associated with the overexpression of the HMGCR gene, thus presenting a novel target for atherosclerosis treatment.
Le texte complet de cet article est disponible en PDF.Keywords : HMGCR gene, Atorvastatin, Diabetic atherosclerosis, Protective effect, Gene silencing, Gene overexpression
Plan
Vol 104
P. 240-251 - août 2018 Retour au numéro
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