LncRNA LncHrt preserves cardiac metabolic homeostasis and heart function by modulating the LKB1-AMPK signaling pathway
Basic Res Cardiol. 2021 Aug 11;116(1):48. doi: 10.1007/s00395-021-00887-3.ABSTRACTMetabolic modulation is a promising therapeutic approach to prevent adverse remodeling of the ischemic heart. Because little is known about the involvement of long non-coding RNAs (lncRNAs) in regulating cardiac metabolism, we used unbiased transcriptome profiling in a mouse model of myocardial infarction (MI). We identified a novel cardiomyocyte-enriched lncRNA, called LncHrt, which regulates metabolism and the pathophysiological processes that lead to heart failure. AAV-based LncHrt overexpression protects the heart from MI as demonstrated by improved contractile function, preserved metabolic homeostasis, and attenuated maladaptive remodeling responses. RNA-pull down followed by mass spectrometry and RNA immunoprecipitation (RIP) identified SIRT2 as a LncHrt-interacting protein involved in cardiac metabolic regulation. Mechanistically, we established that LncHrt interacts with SIRT2 to preserve SIRT2 deacetylase activity by interfering with the CDK5 and SIRT2 interaction. This increases downstream LKB1-AMPK kinase signaling, which ameliorates functional and metabolic deficits. Importantly, we found the expression of the human homolog of mouse LncHrt was decreased in patients with dilated cardiomyopathy. Together, these studies identify LncHrt as a cardiac metabolic regulator that plays an essential role in preserving heart function by regulating downstream metabolic signaling pathways. Consequ...
Source: Cell Research - Category: Cytology Authors: Ning Liu Masaharu Kataoka Yingchao Wang Linbin Pu Xiaoxuan Dong Xuyang Fu Feng Zhang Feng Gao Tian Liang Jianqiu Pei Changchen Xiao Qiongzi Qiu Tingting Hong Qiming Chen Jing Zhao Lianlian Zhu Junhua He Xiaoyun Hu Yu Nie Wei Zhu Hong Yu Douglas B Cowan Xi Source Type: research
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