ANXA1-FPR2 axis mitigates the susceptibility to atrial fibrillation in obesity via rescuing AMPK activity in response to lipid overload
Rattachement africain : cn. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Atrial fibrillation (AF) is the most prevalent arrhythmia in clinical practice, and obesity serves as a significant risk factor for its development. The underlying mechanisms of obesity-related AF remain intricate and have yet to be fully elucidated. We have identified FPR2 as a potential hub gene involved in obesity-related AF through comprehensive analysis of four transcriptome datasets from AF patients and one transcriptome dataset from obese individuals, and its expression is up-regulated in both AF and obese individuals. Interestingly, ANXA1, the endogenous ligand of FPR2, was found to exhibit differential expression with AF and obesity. Specifically, it was observed to be down-regulated in AF patients but up-regulated in obese individuals. The susceptibility to AF in obese mice induced by high-fat diet (HFD) was increased following with the FPR2 blocker Boc-2.The administration of exogenous ANXA1 active peptide chain Ac2-26 can mitigate the susceptibility to AF in obese mice by attenuating atrial fibrosis, lipid deposition, oxidative stress injury, and myocardial cell apoptosis. However, this protective effect against AF susceptibility is reversed by AAV9-shAMPK-mediated AMPK specific knockdown in the myocardium. The vitro experiments demonstrated that silencing ANXA1 exacerbated lipid deposition, oxidative stress injury, and apoptosis induced by palmitic acid (PA) in cardiomyocytes. Additionally, Ac2-26 effectively mitigated myocardial lipid deposition, oxidative stress injury, and apoptosis induced by PA. These effects were impeded by FPR2 inhibitors Boc-2 and WRW4. The main mechanism involves the activation of AMPK by ANXA1 through FPR2 in order to enhance fatty acid oxidation in cardiomyocytes, thereby ultimately leading to a reduction in lipid accumulation and associated lipotoxicity. Our findings demonstrate that the ANXA1-FPR2 axis plays a protective role in obesity-associated AF by alleviating metabolic stress in the atria of obese mice, thereby emphasizing its potential as a promising therapeutic target for AF.
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
- ANXA1-FPR2 axis mitigates the susceptibility to atrial fibrillation in obesity via rescuing AMPK activity in response to lipid overload
- Date Crossref
- 21/12/2024
- Éditeur
- Springer Science and Business Media LLC
- 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
-
Second Affiliated Hospital of Xi'an Jiaotong University pays non établi dans la noticeÉtablissement de santé
-
First Affiliated Hospital of Xi'an Jiaotong University pays non établi dans la noticeÉtablissement de santé
-
Sir Run Run Shaw Hospital Department of Cardiology pays non établi dans la noticeÉtablissement de santé
-
Central South University Department of Cardiology pays non établi dans la noticeUniversité ou école supérieure
-
Third Xiangya Hospital pays non établi dans la noticeÉtablissement de santé
-
Northwestern Polytechnical University pays non établi dans la noticeUniversité ou école supérieure
-
The Second Affiliate Hospital of Xi'an Jiaotong University Department of Cardiology pays non établi dans la noticeUniversité ou école supérieure
-
The First Affiliate Hospital of Xi'an Jiaotong University Department of Endocrinology pays non établi dans la noticeUniversité ou école supérieure
-
School of Life Sciences Xi'an Key Laboratory of Special Medicine and Health Engineering pays non établi dans la noticeUniversité ou école supérieure
Second Affiliated Hospital of Xi'an Jiaotong University, First Affiliated Hospital of Xi'an Jiaotong University et Department of Cardiology — Sir Run Run Shaw Hospital, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.