心力衰竭是众多心血管疾病的终末阶段，而且伴随着 "心肌能量代谢的重编程"，其实质是"心肌能量代谢关键基因的调控"。 我室前期研究发现，miR-29a结合在心肌能量代谢关键基因 PPARδ mRNA 3' 端未翻译区，心肌肥大时其表达升高并诱发心肌肥大发生，而心肌肥大是心力衰竭的独立危险因素。因此，我们提出了"miR-29a通过作用于其靶标蛋白PPARδ在心力衰竭中发挥作用并可能成为心力衰竭标志物"的假说，并拟进行以下研究：首先，根据gain of function 和 loss of function原则，分析miR-29a 通过作用于靶标蛋白PPARδ 对心力衰竭中心功能、血流动力学、心肌病理改变及相关基因表达的影响；其次，分析心力衰竭病人血浆中miR-29a的表达，确定miR-29a能否作为新的心力衰竭标志物。上述研究将进一步阐明心力衰竭的分子机理，为发掘理想的心力衰竭标志物提供线索。

Heart failure is the common end stage of cardiovascular diseases,which accompanied with cardiac energy metabolism reprogramming, and in fact it is reprogramming of the key genes related to cardiac energy metabolism. More recently, we found that miR-29a binds the PPARδ 3' untranslated region, which is an important genes related to cardiac energy metabolism. On the other hand, miR-29a induces cardiac hypertrophy,a separate risk factor for heart failure, and the miR-29a level was increased during cardiac hypertrophy.These data prompted us to address the hypothesis that miR-29a may target PPAR δ to effect on heart failure and can be a potential biomarker for heart failure. We will use mice with gain or loss of miR-29a and/or PPARδ to determine the effects of miR-29a targeting PPAR δ on the cardiac function, hemodynamic, myocardial pathological changes and the expression of heart related genes during heart failure. Next, we will analyze the miR-29a level in plasma of heart failure patients to determine whether miR-29a can be a new potential biomarker for heart failure. These complementary lines of investigation will provide insight to understand the regulatory mechanisms underlying miR-29a and PPARδ in heart failure, which can be exploited for heart failure biomarker to prevent or reverse heart failure.