FYCO1 improves postischemic cardiac remodeling via enhanced autophagic flux and attenuation of proinflammatory signaling
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Le résumé fourni par la source
Abstract Acute myocardial infarction (MI) is associated with severe metabolic and oxidative stress that triggers cardiomyocyte death, pro-inflammatory signaling and progressive structural remodeling frequently culminating in heart failure. Although significant advances in reperfusion therapy improved acute survival in patients, therapeutic strategies that directly target intracellular processes in response to injury remain limited. One key response mechanism, autophagy, is rapidly activated to ameliorate ischemic stress. Yet, defective autophagic flux may exacerbate cardiomyocyte injury and maladaptive tissue remodeling. Here we identify FYCO1 as a cardiomyocyte-enriched key regulator of autophagy that enhances autophagic flux and promotes myocardial resilience following ischemic injury. Using cardiomyocyte-specific FYCO1 transgenic mice subjected to permanent coronary ligation, we demonstrate that FYCO1 overexpression limits infarct expansion, reduces cardiomyocyte injury, and preserves cardiac function during remodeling. In vivo RFP-EGFP-LC3 autophagy reporter analyses reveal that FYCO1 promotes a sustained increase of autophagic flux by coordinating autophagosome formation and efficient autolysosomal clearance. Transcriptomic profiling identifies a cardioprotective gene program in FYCO1-Tg animals subjected to MI, with suppression of proinflammatory, proapoptotic and stress-response pathways. Systemic serum cytokine and chemokine profiling as well as transcriptomic analyses of myocardium confirm reduced inflammatory signaling and subsequent reduction in macrophage recruitment into the infarct border zone. Together these findings position FYCO1 as a key regulator of cardiomyocyte autophagy and reveal a previously unrecognized link between autophagy and inflammation in shaping cardiac remodeling following myocardial infarction. FYCO1-mediated autophagy promotes myocardial preservation and functional recovery, highlighting autophagic flux as a promising target for cardioprotective interventions.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- FYCO1 improves postischemic cardiac remodeling via enhanced autophagic flux and attenuation of proinflammatory signaling
- Date Crossref
- 18/03/2026
- Éditeur
- openRxiv
- Type
- posted-content
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
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Heidelberg University Institute of Experimental Cardiology pays non établi dans la noticeUniversité ou école supérieure
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University Hospital Heidelberg Department of Internal Medicine III pays non établi dans la noticeÉtablissement de santé
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German Centre for Cardiovascular Research pays non établi dans la noticeStructure de recherche
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University Hospital Schleswig-Holstein Department of Internal Medicine V pays non établi dans la noticeÉtablissement de santé
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University of Lübeck pays non établi dans la noticeUniversité ou école supérieure
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Helmholtz Association of German Research Centres pays non établi dans la noticeOrganisme public
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DZHK (German Center for Cardiovascular Research) pays non établi dans la noticeInstitution
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Medical Faculty Mannheim Department of Cardiovascular Physiology pays non établi dans la noticeUniversité ou école supérieure
Institute of Experimental Cardiology — Heidelberg University, Department of Internal Medicine III — University Hospital Heidelberg et German Centre for Cardiovascular Research, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.