miR-29a attenuates cardiac hypertrophy through inhibition of PPARδ expression
miR-29a attenuates cardiac hypertrophy through inhibition of PPARδ expression
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miR-29a 通过抑制 PPARδ 表达减轻心脏肥大
DOI：
10.1002/jcp.27997
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Xue L
中科院分区：
文献类型：
--
作者：
Zhang S;Yin Z;Dai FF;Wang H;Zhou MJ;Yang MH;Zhang SF;Fu ZF;Mei YW;Zang MX;Xue L
虽然心脏肥大被广泛认为是导致心功能障碍并最终导致心力衰竭的危险因素，但心脏肥大的复杂机制仍不完全。核受体过氧化物酶体增殖物激活受体δ（PPARδ）参与心脏脂质代谢的调节。在这里，我们描述了一种新的PPARδ依赖性分子级联反应，涉及microRNA-29 a（miR-29 a）和心钠素（ANF），在心肌肥厚中重新激活。此外，我们确定了miR-29 a的一种新作用，即它通过靶向PPARδ和下调ANF在盐酸异丙肾上腺素诱导的心脏肥大中具有心脏保护功能。最后，我们提供的证据表明，miR-29 a减少了盐酸异丙肾上腺素诱导的心脏肥大反应，从而强调了miR-29 a的潜在临床相关性，其中它可能作为心脏肥大治疗的有效治疗靶点。
Although cardiac hypertrophy is widely recognized as a risk factor that leads to cardiac dysfunction and, ultimately, heart failure, the complex mechanisms underlying cardiac hypertrophy remain incompletely characterized. The nuclear receptor peroxisome proliferator‐activated receptor δ (PPARδ) is involved in the regulation of cardiac lipid metabolism. Here, we describe a novel PPARδ‐dependent molecular cascade involving microRNA‐29a (miR‐29a) and atrial natriuretic factor (ANF), which is reactivated in cardiac hypertrophy. In addition, we identify a novel role of miR‐29a, in which it has a cardioprotective function in isoproterenol hydrochloride‐induced cardiac hypertrophy by targeting PPARδ and downregulating ANF. Finally, we provide evidence that miR‐29a reduces the isoproterenol hydrochloride‐induced cardiac hypertrophy response, thereby underlining the potential clinical relevance of miR‐29a in which it may serve as a potent therapeutic target for heart hypertrophy treatment.