Simvastatin Treatment Protects Myocardium in Noncoronary Artery Cardiac Surgery by Inhibiting Apoptosis Through miR-15a-5p Targeting
| Autor: | Mao-Mao Shi, Tian-Pu Cheng, Ying-Qi Xu, Michael J. Quon, Zhi-Jun Ou, Xi Zhang, Chen Liu, Chun-Xiang Zhang, Yu-Peng Jian, Hua-Ming Li, Zhi-Ping Wang, Zhe Xu, Xiang Liu, Yan Li, Zhen-Qing Wang, Jing-Song Ou, Li Zhou, Wen Zhang |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine China Simvastatin Heart Diseases Microarray Apoptosis 030204 cardiovascular system & hematology Pharmacology Drug Administration Schedule Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine microRNA Animals Humans Medicine Myocyte Myocytes Cardiac Cells Cultured Messenger RNA TUNEL assay business.industry Middle Aged MicroRNAs Treatment Outcome bcl-2 Homologous Antagonist-Killer Protein 030104 developmental biology medicine.anatomical_structure Proto-Oncogene Proteins c-bcl-2 Elective Surgical Procedures Female Hydroxymethylglutaryl-CoA Reductase Inhibitors Cardiology and Cardiovascular Medicine business Signal Transduction Artery medicine.drug |
| Zdroj: | Journal of Cardiovascular Pharmacology. 72:176-185 |
| ISSN: | 0160-2446 2529-2536 |
| DOI: | 10.1097/fjc.0000000000000611 |
| Popis: | Simvastatin treatment is cardioprotective in patients undergoing noncoronary artery cardiac surgery. However, the mechanisms by which simvastatin treatment protects the myocardium under these conditions are not fully understood. Seventy patients undergoing noncoronary cardiac surgery, 35 from a simvastatin treatment group and 35 from a control treatment group, were enrolled in our clinical study. Simvastatin (20 mg/d) was administered preoperatively for 5-7 days. Myocardial tissue biopsies were taken before and after surgery. Apoptosis was detected by TUNEL staining. The expressions of Bcl-2 and Bak in myocardial tissue were detected by immunoblotting. The expressions of miRNA and Bcl-2 mRNA were detected by quantitative real-time polymerase chain reaction assays. Cardiomyocytes were isolated from rat and cultured cells. MiR-15a-5p mimic was transfected into cardiomyocytes, and the Bcl-2 was detected by immunoblotting. TUNEL staining showed significantly less myocardial apoptosis in the simvastatin treatment group when compared with the control treatment group. Protein expression of Bcl-2 was increased in the simvastatin treatment group before surgery, and Bak expression was increased in the control treatment group after surgery. Further comparisons showed that Bcl-2/Bak ratios were reduced in the control treatment group but were not significantly changed in the simvastatin treatment group after surgery. Furthermore, microarray assays revealed that miR-15a-5p was significantly decreased by simvastatin treatment. This was validated by quantitative real-time polymerase chain reaction analysis. MiR-15a-5p was predicted to target Bcl-2 mRNA at nucleotide positions 2529-2536. This was validated by luciferase binding assays. Coincident with the change in miR-15a-5p, the mRNA expression of Bcl-2 was increased in the simvastatin treatment group. MiR-15a-5p mimic significantly inhibited Bcl-2 expression in cardiomyocytes. Our findings strongly suggest that simvastatin treatment preoperatively protected the myocardium in patients undergoing noncoronary artery cardiac surgery, at least in part, by inhibiting apoptosis via suppressing miR-15a-5p expression, leading to increasing expression of Bcl-2 and decreasing expression of Bak. |
| Databáze: | OpenAIRE |
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