Regulation of lovastatin on a key inflammation-related microRNA in myocardial cells

• Published in: Chinese medical journal 2014, Vol.127 (16), p.2977-2981
• Main Authors: Guo, Weizao, Liu, Huichen, Li, Lin, Yang, Man, Du, Aihua
• Format: Article
• Language: English
• Subjects: Blotting, Western; Cell Line; Humans; Lipopolysaccharides - pharmacology; Lovastatin - pharmacology; MicroRNAs - genetics; Myocardium - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Phosphoprotein Phosphatases - metabolism; Phosphorylation; STAT3; STAT3 Transcription Factor - metabolism; 微RNA; 心肌细胞; 心血管疾病; 洛伐他汀; 炎症; 联合治疗; 聚合酶链式反应
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.20140780

Background Advances in the understanding of cardiovascular pathogenesis have highlighted that inflammation plays a central role in athemsclemtic coronary heart disease.Therefore,exploring pharmacologically based anti-inflammatory treatments to be used in cardiovascular therapeutics is worthwhile to promote the discovery of novel ways of treating cardiovascular disorders.Methods The myocardial cell line H9c2（2-1） was exposed to lipopolysacchadde （LPS） in culture and resulted in a cellular pro-inflammation status,miR-21 microRNA levels were detected using quantitative real-time polymerase chain reaction （Q-RT-PCR）.The influence of Iovastatin on miR-21 under normal and pro-inflammatory conditions was tested after being added to the cell culture mixture for 24 hours.Conditional gene function of two predicted cardiovascular system relevant downstream targets of miR-21,protein phosphatase 1 regulatory subunit 3A （PPP1R3A） and signal transducer and activator of transcription 3 （STAT3）,were analyzed with immunoblotting.Results Forty-eight hours of LPS treatment significantly increased the miR-21 to 170.71%±34.32% of control levels （P=0.002）.Co-treatment with Iovastatin for 24 hours before harvesting attenuated the up-regulation of miR-21 （P=0.013）.Twenty-four hours of Iovastatin exposure up-regulated PPP1R3A to 143.85%±21.89% of control levels in cardiomyocytes （P=0.023）.Lovastatin up-regulated the phosphorylation level of STAT3 compared to the background LPS pretreatment （P=0.0077）,this effect was significantly （P=0.018） blunted when miR-21 was functionally inhibited.Conclusions miR-21 plays a major role in the regulation of the cellular anti-inflammation effects of Iovastatin.