Liu 2021 Basic Res Cardiol

From Bioblast
Publications in the MiPMap
Liu N, Kataoka M, Wang Y, Pu L, Dong X, Fu X, Zhang F, Gao F, Liang T, Pei J, Xiao C, Qiu Q, Hong T, Chen Q, Zhao J, Zhu L, He J, Hu X, Nie Y, Zhu W, Yu H, Cowan DB, Hu X, Wang J, Wang DZ, Chen J (2021) LncRNA LncHrt preserves cardiac metabolic homeostasis and heart function by modulating the LKB1-AMPK signaling pathway. Basic Res Cardiol 116:48.

Β» PMID: 34379189 Open Access

Liu Ning, Kataoka Masaharu, Wang Yingchao, Pu Linbin, Dong Xiaoxuan, Fu Xuyang, Zhang Feng, Gao Feng, Liang Tian, Pei Jianqiu, Xiao Changchen, Qiu Qiongzi, Hong Tingting, Chen Qiming, Zhao Jing, Zhu Lianlian, He Junhua, Hu Xiaoyun, Nie Yu, Zhu Wei, Hong Yu Hong, Cowan Douglas B, Hu Xinyang, Wang Jian'an, Wang Da-Zhi, Chen Jinghai (2021) Basic Res Cardiol

Abstract: Metabolic 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. Consequently, LncHrt is a potentially novel RNA-based therapeutic target for ischemic heart disease. β€’ Keywords: CDK5, Cardiac metabolic homeostasis, Cardiac remodeling, LKB1-AMPK kinase cascade, LncRNA, SIRT2, Therapeutic target β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: CN Hangzhou Zhu W

Labels: MiParea: Respiration, Genetic knockout;overexpression  Pathology: Cardiovascular 

Organism: Mouse  Tissue;cell: Heart  Preparation: Permeabilized tissue 

Coupling state: OXPHOS  Pathway: F, N, S, CIV, ROX  HRR: Oxygraph-2k 

CN, 2021-09 

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