Renalase improves pressure overload-induced heart failure in rats by regulating extracellular signal-regulated protein kinase 1/2 signaling
Renalase improves pressure overload-induced heart failure in rats by regulating extracellular signal-regulated protein kinase 1/2 signaling
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肾酶通过调节细胞外信号调节蛋白激酶 1/2 信号传导改善压力超负荷诱导的大鼠心力衰竭
DOI：
10.1038/s41440-020-00599-6
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发表时间：
2021-01-08
影响因子：
5.4
通讯作者：
Li, Xiaogang
中科院分区：
文献类型：
--
作者：
Wu, Yuyan;Quan, Chengxuan;Li, Xiaogang
肾氨酸酶是一种新的黄素蛋白，主要在肾脏和心脏表达，在高血压中起着关键作用。最近的研究表明，肾酶在心力衰竭患者血清中的表达水平较低，但其在心力衰竭中的作用及其机制尚不清楚。采用成年SD大鼠，研究肾酶在横动脉缩窄(TAC)所致心力衰竭病理过程中的作用。肾氨酸酶-人蛋白芯片分析表明肾氨酸酶与P38和细胞外信号调节蛋白激酶1/2(ERK1/2)信号转导直接相关。我们进一步利用慢病毒介导的RNA干扰来研究肾酶在病理性心室肥厚进展中的作用，发现肾酶抑制在体外减弱了去甲肾上腺素诱导的肥厚反应或在体内减弱了压力超负荷诱导的肥厚反应。重组肾酶蛋白显著减轻压力超负荷所致的心力衰竭，并与P38和ERK1/2信号转导有关。这些发现表明肾酶是一个潜在的肥厚生物标志物，外源性重组肾酶是一种潜在的治疗心力衰竭的新药。
Renalase, a novel flavoprotein that is mainly expressed in the kidney and heart, plays a crucial role in hypertension. Recent studies have shown that renalase is expressed at low levels in the serum of patients with heart failure, while the role of renalase and its mechanism in cardiac failure is unclear. Adult Sprague-Dawley (SD) rats were used to investigate the role and function of renalase in the pathological process of transverse aortic constriction (TAC)-induced heart failure. Renalase-human protein chip analysis showed that renalase was directly associated with P38 and extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling. We further used lentivirus-mediated RNA interference to study the role of renalase in the progression of pathological ventricular hypertrophy and found that renalase inhibition attenuated the noradrenaline-induced hypertrophic response in vitro or the pressure overload-induced hypertrophic response in vivo. Recombinant renalase protein significantly alleviated pressure overload-induced cardiac failure and was associated with P38 and ERK1/2 signaling. These findings demonstrate that renalase is a potential biomarker of hypertrophy and that exogenous recombinant renalase is a potential and novel drug for heart failure.