Free radical biology & medicine · 2026
Myeloid specific knockout of Piezo1 alleviates ang Ⅱ-induced cardiac remodeling.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Ошибки и ограничения
История · было → стало
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Liu Jiali, Niu Weipin, Xu Pangao, Guo Haonan, Zhao Ying, Hong Tianying, Luo Shangfei, Wang Panyu, Sun Xin, Chen Xiaoting, Li Jing
Аннотация
INTRODUCTION: Cardiac remodeling in heart failure is closely associated with macrophage-mediated immune responses. The mechanosensitive ion channel Piezo1, which is abundantly expressed in macrophages, has been implicated in mechanically driven cardiovascular pathologies. However, the specific function of macrophage Piezo1 in pathological cardiac remodeling remains unclear.
OBJECTIVE: Here, we aimed to investigate the potential regulation of heart failure by Piezo1 and delineate its underlying mechanosensitive signaling pathways.
METHODS: We induced heart failure via chronic angiotensin Ⅱ (Ang Ⅱ) infusion in male Piezo1fl/fl and myeloid-specific Piezo1 knockout (Piezo1ΔLysM) mice. Cardiac function and pathological changes were assessed using echocardiography, histology and molecular assays.
RESULTS: Piezo1 expression was markedly upregulated in mouse hearts following Ang Ⅱ infusion. Myeloid Piezo1 deficiency mitigated Ang Ⅱ-induced cardiac dysfunction, hypertrophy, fibrosis, and inflammation. Consistent with in vivo data, Piezo1 knockout reduced Ang Ⅱ-induced inflammatory responses and altered macrophage polarization in vitro. Mechanistically, Piezo1 aggravated disease progression by increasing Ca2+ entry and activating CaMKⅡ, which drove cytoskeletal remodeling and promoted YAP/TAZ nuclear translocation in macrophages. Consequently, myeloid Piezo1 deficiency suppressed Ang Ⅱ-induced inflammatory responses and downstream intercellular crosstalk with cardiomyocytes and fibroblasts.
CONCLUSION: Collectively, myeloid Piezo1 deficiency attenuates heart failure by restraining YAP/TAZ nuclear translocation in macrophages via a Ca2+/CaMKⅡ-dependent cytoskeletal remodeling pathway. This study suggests that Piezo1 may represent a promising therapeutic target for hypertension-associated heart failure.
OBJECTIVE: Here, we aimed to investigate the potential regulation of heart failure by Piezo1 and delineate its underlying mechanosensitive signaling pathways.
METHODS: We induced heart failure via chronic angiotensin Ⅱ (Ang Ⅱ) infusion in male Piezo1fl/fl and myeloid-specific Piezo1 knockout (Piezo1ΔLysM) mice. Cardiac function and pathological changes were assessed using echocardiography, histology and molecular assays.
RESULTS: Piezo1 expression was markedly upregulated in mouse hearts following Ang Ⅱ infusion. Myeloid Piezo1 deficiency mitigated Ang Ⅱ-induced cardiac dysfunction, hypertrophy, fibrosis, and inflammation. Consistent with in vivo data, Piezo1 knockout reduced Ang Ⅱ-induced inflammatory responses and altered macrophage polarization in vitro. Mechanistically, Piezo1 aggravated disease progression by increasing Ca2+ entry and activating CaMKⅡ, which drove cytoskeletal remodeling and promoted YAP/TAZ nuclear translocation in macrophages. Consequently, myeloid Piezo1 deficiency suppressed Ang Ⅱ-induced inflammatory responses and downstream intercellular crosstalk with cardiomyocytes and fibroblasts.
CONCLUSION: Collectively, myeloid Piezo1 deficiency attenuates heart failure by restraining YAP/TAZ nuclear translocation in macrophages via a Ca2+/CaMKⅡ-dependent cytoskeletal remodeling pathway. This study suggests that Piezo1 may represent a promising therapeutic target for hypertension-associated heart failure.