PIEZO1 gain-of-function mutation drives cardiomyopathy by disrupting myocardial lipid homeostasis besides iron overload
Rattachement africain : cn, th. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
As a mechanosensitive channel, PIEZO1 translates mechanical stretching of cardiomyocytes into Ca 2+ signaling, underpinning the Frank-Starling law. This mechanism contributes to compensatory responses in heart failure. However, the relationship between PIEZO1 mutations and the development of cardiomyopathy remains unclear. Acute heart failure complicated with severe myocardial iron deposition was identified in the 31-year-old male proband of PIEZO1 D669Y variant. However, PIEZO1 gain-of-function (GOF) mutation D674Y mice and cardiomyocyte-specific Piezo1 overexpression disrupted cardiac function besides iron overload. Using single-cell RNA sequencing, we observed suppression of lipid metabolism pathways in cardiomyocytes with the PIEZO1 GOF mutation, with forkhead box O3 (FOXO3) as a key mediator in lipid metabolism pathways. Specifically, the PIEZO1 GOF mutation increased Ca 2+ levels, leading to calcium- and calmodulin-dependent protein kinase II (CaMKII) activation and subsequent FOXO3 down-regulation. Together, we demonstrate that PIEZO1 GOF mutation contributes to cardiomyopathy by disrupting myocardial lipid metabolism. This study challenges the current clinical focus on iron-related mechanisms in cardiomyopathy and supports PIEZO1 as a potential candidate for future genetic screening for cardiomyopathy.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- PIEZO1 gain-of-function mutation drives cardiomyopathy by disrupting myocardial lipid homeostasis besides iron overload
- Date Crossref
- 14/11/2025
- Éditeur
- American Association for the Advancement of Science (AAAS)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Chinese Academy of Medical Sciences & Peking Union Medical College pays non établi dans la noticeUniversité ou école supérieure
-
Ministry of Education Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine pays non établi dans la noticeOrganisme public
-
Qilu Hospital of Shandong University Department of Emergency Medicine pays non établi dans la noticeÉtablissement de santé
-
Fudan University Institutes of Biomedical Sciences pays non établi dans la noticeUniversité ou école supérieure
-
Zhongshan Hospital pays non établi dans la noticeÉtablissement de santé
-
Institute of Emergency and Critical Care Medicine of Shandong University Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine pays non établi dans la noticeUniversité ou école supérieure
Chinese Academy of Medical Sciences & Peking Union Medical College, Medical and Pharmaceutical Basic Research Innovation Center of Emergency and Critical Care Medicine — Ministry of Education et Department of Emergency Medicine — Qilu Hospital of Shandong University, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.