Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Chenxing Huang
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Xuejuan Jin
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Jian Wu
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; NHC Key Laboratory of Ischemic Heart Diseases, and Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, China
Kejia Jin
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Jingyi Lin
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Ying Wang
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Jianxuan Li
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Chao Yin
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Xiang Wang
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Lei Zhang
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Guoping Zhang
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China
Hangming Dong
Department of Respiratory and Critical Care Medicine, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China
Junli Guo
Key Laboratory of Tropical Translational Medicine of Ministry of Education & Hainan Provincial Key Laboratory for Tropical Cardiovascular Diseases Research, School of Public Health, Hainan Medical University, Haikou, 571199, China
Issei Komuro
Department of Frontier Cardiovascular Science, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan
Yuxiang Dai
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; NHC Key Laboratory of Ischemic Heart Diseases, and Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, China; Corresponding author. Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Yunzeng Zou
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; NHC Key Laboratory of Ischemic Heart Diseases, and Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, China; Corresponding author. Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Hui Gong
Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China; NHC Key Laboratory of Ischemic Heart Diseases, and Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, China; Corresponding author. Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China.
Sustained myocardial hypertrophy or left ventricular hypertrophy (LVH) triggered by pressure overload is strongly linked to adverse cardiovascular outcomes. Here, we investigated the clinical relationship between serum HSP90α (an isoform of HSP90) levels and LVH in patients with hypertension or aortic stenosis (AS) and explored underlying mechanisms in pressure overload mouse model. We built a pressure overload mouse model via transverse aortic constriction (TAC). Compared to controls, elevated serum HSP90α levels were observed in patients with hypertension or AS, and the levels positively correlated with LVH. Similarly, HSP90α levels increased in heart tissues from patients with obstructive hypertrophic cardiomyopathy (HCM), and in mice post-TAC. TAC induced the enhanced cardiac expression and secretion of HSP90α from cardiomyocytes and cardiac fibroblasts. Knockdown of HSP90α or blockade of extracellular HSP90α (eHSP90α) attenuated cardiac hypertrophy and dysfunction by inhibition of β-catenin/TCF7 signaling under pressure overload. Further analysis revealed that eHSP90α interacted with EC1-EC2 region of N-cadherin to activate β-catenin, enhancing the transcription of hypertrophic genes by TCF7, resulting in cardiac hypertrophy and dysfunction under pressure overload. These insights suggest the therapeutic potential of targeting HSP90α-initiated signaling pathway against cardiac hypertrophy and heart failure under pressure overload.
