Increasing evidence shows that miRNAs play pivotal roles in cardiovascular diseases, including heart failure (HF). The aim of this study was to investigate the role of miR-129-5p in chronic heart failure and the underlying mechanisms. The levels of miR-129-5p and HMGB1 in chronic heart failure patients (CHF) and normal controls were examined by RT-qPCR and ELISA. Cardiac function, hemodynamics parameters, oxidative stress, and inflammation factors were analyzed in CHF rat model after transfection of miR-129-5p or HMGB1. Dual-luciferase activity reporter assay was conducted to validate the interaction between miR-129-5p and HMGB1. Downregulation of miR-129-5p and upregulation of HMGB1 were observed in the serum of CHF patients, respectively. Transfection of miR-129-5p improved heart function and hemodynamic parameters, as well as attenuated oxidative stress and inflammation factors in CHF rats. We further confirmed that HMGB1 is a direct target of miR-129-5p. Transfection of miR-129-5p also decreased the mRNA and protein levels of HMGB1 in myocardial tissues of CHF rats. Overexpression of HMGB1 diminished the effects of miR-129-5p on ameliorating oxidative stress and inflammatory response in rats with CHF. Our findings suggest that miR-129-5p protects the heart by targeting HMGB1.

中文翻译：

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miR-129-5p通过靶向HMGB1改善慢性心力衰竭大鼠的心脏功能。

越来越多的证据表明，miRNA在包括心力衰竭（HF）在内的心血管疾病中起着关键作用。这项研究的目的是调查miR-129-5p在慢性心力衰竭中的作用及其潜在机制。通过RT-qPCR和ELISA检测慢性心力衰竭患者（CHF）和正常对照组中miR-129-5p和HMGB1的水平。转染miR-129-5p或HMGB1后，在CHF大鼠模型中分析了心脏功能，血液动力学参数，氧化应激和炎症因子。进行了双重荧光素酶活性报告基因测定，以验证miR-129-5p与HMGB1之间的相互作用。在CHF患者的血清中分别观察到miR-129-5p的下调和HMGB1的上调。转染miR-129-5p可改善心脏功能和血液动力学参数，以及CHF大鼠的氧化应激和炎症因子减弱。我们进一步证实，HMGB1是miR-129-5p的直接靶标。miR-129-5p的转染也降低了CHF大鼠心肌组织中HMGB1的mRNA和蛋白水平。HMGB1的过表达减少了miR-129-5p对CHF大鼠氧化应激和炎症反应的缓解作用。我们的发现表明，miR-129-5p通过靶向HMGB1来保护心脏。