Variations in Energy Metabolism Precede Alterations in Cardiac Structure and Function in Hypertrophic Preconditioning

Frontiers in Cardiovascular Medicine

article

Jian Wu¹  Jing Lu¹  Jiayuan Huang²  Jieyun You³  Zhiwen Ding¹  Leilei Ma¹  Fangjie Dai¹  Ran Xu¹  Xuan Li¹  Peipei Yin¹  Gang Zhao¹  Shijun Wang¹  Jie Yuan¹  Xiangdong Yang¹  Junbo Ge¹  Yunzeng Zou¹ 

[1] Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University;Key Laboratory of Guangdong Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute;Department of Cardiovascular Medicine, Shanghai East Hospital, Tongji University School of Medicine

关键词: cardiac function;    cardiac hypertrophy;    hypertrophic preconditioning;    metabolism;    pressure overload;   

DOI  :  10.3389/fcvm.2020.602100

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

Recent studies have unveiled that myocardial hypertrophic preconditioning (HP), which is produced by de-banding (De-TAC) of short-term transverse aortic constriction (TAC), protects the heart against hypertrophic responses caused by subsequent re-constriction (Re-TAC) in mice. Although cardiac substrate metabolism is impaired in heart failure, it remains unclear about the role of HP-driven energetics in the development of cardiac hypertrophy. Here, we investigated energy metabolism, cardiac hypertrophy, and function following variational loading conditions, as well as their relationships in HP. Male C57BL/6J mice (10–12 weeks old) were randomly subjected to Sham, HP [TAC for 3days (TAC 3d), de-banding the aorta for 4 days (De-TAC 4d), and then re-banding the aorta for 4 weeks (Re-TAC 4W)], and TAC (TAC for 4 weeks without de-banding). Cardiac echocardiography, hemodynamics, and histology were utilized to evaluate cardiac remodeling and function. The mRNA expression levels of fetal genes ( ANP and BNP ), glucose metabolism-related genes ( glut4, pdk4 ), and fatty acid oxidation-related genes ( mcad, pgc1 α, mcd, ppar α) were quantitated by real-time quantitative PCR. Activation of hypertrophy regulators ERK1/2, a metabolic stress kinase AMP-activated protein kinase (AMPK), and its downstream target acetyl-coA carboxylase (ACC) were explored by western blot. Compared with TAC 4W mice, Re-TAC 4W mice showed less impairment in glucose and fatty acid metabolism, as well as less cardiac hypertrophy and dysfunction. Moreover, no significant difference was found in myocardial hypertrophy, fibrosis, and cardiac function in TAC 3d and De-TAC 4d groups compared with Sham group. However, glut4, pdk4, mcad, pgc1 α, mcd , and ppar α were all decreased, while AMPK and ACC were activated in TAC 3d and returned to Sham level in De-TAC 4d, suggesting that the change in myocardial energy metabolism in HP mice was earlier than that in cardiac structure and function. Collectively, HP improves energy metabolism and delays cardiac remodeling, highlighting that early metabolic improvements drive a potential beneficial effect on structural and functional restoration in cardiac hypertrophy.

【 授权许可】

CC BY