Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failure
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 aort...
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Elsevier
2025-02-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231724004440 |
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| author | Le Pan Chenxing Huang Xuejuan Jin Jian Wu Kejia Jin Jingyi Lin Ying Wang Jianxuan Li Chao Yin Xiang Wang Lei Zhang Guoping Zhang Hangming Dong Junli Guo Issei Komuro Yuxiang Dai Yunzeng Zou Hui Gong |
| author_facet | Le Pan Chenxing Huang Xuejuan Jin Jian Wu Kejia Jin Jingyi Lin Ying Wang Jianxuan Li Chao Yin Xiang Wang Lei Zhang Guoping Zhang Hangming Dong Junli Guo Issei Komuro Yuxiang Dai Yunzeng Zou Hui Gong |
| author_sort | Le Pan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9cbf8c5d060e48679e0587a52d3287c5 |
| institution | Kabale University |
| issn | 2213-2317 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj-art-9cbf8c5d060e48679e0587a52d3287c52025-01-14T04:12:10ZengElsevierRedox Biology2213-23172025-02-0179103466Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failureLe Pan0Chenxing Huang1Xuejuan Jin2Jian Wu3Kejia Jin4Jingyi Lin5Ying Wang6Jianxuan Li7Chao Yin8Xiang Wang9Lei Zhang10Guoping Zhang11Hangming Dong12Junli Guo13Issei Komuro14Yuxiang Dai15Yunzeng Zou16Hui Gong17Shanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaShanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaShanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaShanghai 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, ChinaShanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaShanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaShanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaShanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaShanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaShanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaShanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaShanghai Institute of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Diseases, Zhongshan Hospital, and Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, ChinaDepartment of Respiratory and Critical Care Medicine, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, ChinaKey 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, ChinaDepartment of Frontier Cardiovascular Science, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, JapanShanghai 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.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.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.http://www.sciencedirect.com/science/article/pii/S2213231724004440HSP90Cardiac hypertrophyPressure overloadHeart failureβ-catenin |
| spellingShingle | Le Pan Chenxing Huang Xuejuan Jin Jian Wu Kejia Jin Jingyi Lin Ying Wang Jianxuan Li Chao Yin Xiang Wang Lei Zhang Guoping Zhang Hangming Dong Junli Guo Issei Komuro Yuxiang Dai Yunzeng Zou Hui Gong Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failure Redox Biology HSP90 Cardiac hypertrophy Pressure overload Heart failure β-catenin |
| title | Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failure |
| title_full | Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failure |
| title_fullStr | Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failure |
| title_full_unstemmed | Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failure |
| title_short | Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failure |
| title_sort | cardiac secreted hsp90α exacerbates pressure overload myocardial hypertrophy and heart failure |
| topic | HSP90 Cardiac hypertrophy Pressure overload Heart failure β-catenin |
| url | http://www.sciencedirect.com/science/article/pii/S2213231724004440 |
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