Inhibition of microRNA-146a attenuated heart failure in myocardial infarction rats
Inhibition of microRNA-146a attenuated heart failure in myocardial infarction rats
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DOI：
10.1042/bsr20191732
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发表时间：
2019-12-23
影响因子：
4
通讯作者：
Li, Yong
中科院分区：
文献类型：
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作者：
He, Junjie;Lu, Ying;Li, Yong
本研究的目的是确定microRNA(MiR)-146a在心肌梗死(MI)诱导的心力衰竭和心脏重构中的作用。实验在结扎左冠状动脉诱发心力衰竭的SD大鼠、新生大鼠心脏成纤维细胞(CFs)和血管紧张素II(Ang)II处理的心肌细胞上进行。注射2周后处死大鼠。心肌梗死大鼠左室射血分数和短轴缩短率降低，舒张期和收缩期室壁容量增加，miR-146a拮抗剂逆转这种作用，miR-146aagomiR治疗后进一步加重。应用miR-146a拮抗剂后，MI大鼠的LV+/-dp/dt(Max)和LV收缩压(LVSP)降低，LVEDP升高，而miR-146a拮抗剂使MI大鼠LV+/-dp/dt(Max)、LVSP和LVEDP恶化。MiR-146a拮抗剂可抑制MI大鼠心房利钠肽(ANP)、脑利钠肽(BNP)、I型胶原和III型胶原，以及血清ST2和去甲肾上腺素水平的升高，而用miR-146a拮抗剂治疗后则加重。MiR-146a拮抗剂可抑制Ang II诱导的CFs胶原I、III型水平升高，Ang II诱导的心肌细胞ANP、BNP水平升高，而miR-146aagomiR则加重Ang II引起的心肌细胞ANP、BNP水平升高。这些结果表明，抑制miR-146a可以改善心力衰竭大鼠的心功能障碍和心脏重构。
The aim of the present study was to determine the roles of microRNA (miR)-146a on myocardial infarction (MI)-induced heart failure and cardiac remodeling. Experiments were carried out in Sprague-Dawley rats treated with ligation of left coronary artery to induce heart failure, and in primary neonatal rat cardiac fibroblasts (CFs) and cardiomyocytes treated with angiotensin (Ang) II. Four weeks after MI, rats were injected with miR-146a antagomiR or agomiR via tail vein. After 2 weeks of injection, the rats were killed. In MI rats, left ventricle (LV) ejection fraction and fractional shortening were reduced, and LV volumes in diastole and systole were increased, which were reversed by miR-146a antagomiR, and further exacerbated after miR-146a agomiR treatment. Administration of miR-146a antagomiR improved the decreases of LV +/-dp/dt(max) and LV systolic pressure (LVSP), and the increase in LV end-diastolic pressure (LVEDP) of MI rats, but miR-146a agomiR deteriorated the LV +/-dp/dt(max), LVSP and LVEDP. The increases in the levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), collagen I and collagen III in the heart, and ST2 and norepinephrine in the serum of MI rats were inhibited by miR-146a antagomiR, but aggravated after miR-146a agomiR treatment. The increases of collagen I and collagen III levels induced by Ang II in CFs, and the increases of ANP and BNP levels induced by Ang II in cardiomyocytes were inhibited by miR-146a antagomiR, but aggravated by miR-146a agomiR. These results demonstrated that inhibition of miR-146a improved cardiac dysfunction and cardiac remodeling in heart failure rats.