HypERlnc attenuates angiotensin II-induced cardiomyocyte hypertrophy via promoting SIRT1 SUMOylation-mediated activation of PGC-1α/PPARα pathway in AC16 cells
HypERlnc attenuates angiotensin II-induced cardiomyocyte hypertrophy via promoting SIRT1 SUMOylation-mediated activation of PGC-1α/PPARα pathway in AC16 cells
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HypERlnc 通过促进 AC16 细胞中 SIRT1 SUMOylation 介导的 PGC-1α/PPARα 通路激活来减弱血管紧张素 II 诱导的心肌细胞肥大
DOI：
10.1002/cbin.12001
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Dong Z
中科院分区：
文献类型：
--
作者：
Yue L;Sheng S;Yuan M;Lu J;Li T;Shi Y;Dong Z
心脏肥大是全球心血管死亡率的一个公认风险因素。根据最近的一项研究，与健康对照相比，心力衰竭（HF）患者左心室心肌中缺氧诱导的内质网应激调节长链非编码RNA（HypERlnc）显著减少。然而，HypERlnc对肥大的影响尚不清楚。在这项研究中，HypERlnc在慢性HF患者血清中的表达水平进行了分析。并探讨HypERlnc对心肌细胞肥大的保护作用及其机制。在此，在HF患者的血清和血管紧张素II（Ang II）刺激的AC 16细胞中，HypERlnc表达水平降低。在Ang II诱导的心肌细胞肥大中，HypERlnc过表达可减小细胞大小并抑制肥大基因（ANP、BNP和β-MHC）的表达。同时，HypERlnc可通过上调PGC-1α/PPARα信号通路，改善Ang II诱导的能量代谢障碍和线粒体损伤。此外，发现SIRT 1 SUMO化介导了HypERlnc诱导的心肌细胞肥大抑制和能量代谢改善。综上所述，本研究表明HypERlnc通过增强SIRT 1蛋白的SUMO化来抑制心肌细胞肥大和能量代谢功能障碍。HypERlnc是预防和治疗病理性心肌肥厚的潜在新分子靶点。
Cardiac hypertrophy is a well‐established risk factor for cardiovascular mortality worldwide. According to a recent study, hypoxia‐induced endoplasmic reticulum stress regulating long noncoding RNA (HypERlnc) is significantly reduced in the left ventricular myocardium of heart failure (HF) patients compared with healthy controls. However, the effect of HypERlnc on hypertrophy is unclear. In this study, the expression level of HypERlnc in serum of patients with chronic HF was analyzed. Moreover, the cardioprotective effect and mechanism of HypERlnc against cardiomyocyte hypertrophy were explored. Here, the level of HypERlnc expression was reduced in serum of patients with HF and in Angiotensin II (Ang II)‐stimulated AC16 cells. HypERlnc overexpression could reduce cell size and inhibit expression of hypertrophy genes (ANP, BNP, and β‐MHC) in the Ang II‐induced cardiomyocyte hypertrophy. Meanwhile, HypERlnc could improve the Ang II‐induced energy metabolism dysfunction and mitochondrial damage via upregulating PGC‐1α/PPARα signaling pathway. Furthermore, it is found that SIRT1 SUMOylation mediated the HypERlnc‐induced inhibition of cardiomyocyte hypertrophy and the improvement of energy metabolism. Taken together, this study suggests that HypERlnc suppresses cardiomyocyte hypertrophy and energy metabolism dysfunction via enhancing SUMOylation of SIRT1 protein. HypERlnc is a potential novel molecular target for preventing and treating pathological cardiac hypertrophy.