CTLA-4-Ig therapy preserves cardiac function following myocardial infarction with reperfusion
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Le résumé fourni par la source
AIMS: T cells drive adverse cardiac inflammation and ischemia-reperfusion injury following myocardial infarction (MI). Here, we aimed to test the extent to which T cell inhibition protected cardiac function following MI in mice. METHODS AND RESULTS: Cardiac ischemia-reperfusion injury (CIRI), mimicking MI with successful reperfusion therapy, was induced in C57BL/6J mice via temporary surgical ligation of the left anterior descending artery. T cell inhibition was achieved using abatacept, an FDA-approved CTLA-4-Ig fusion protein. Multiple treatment strategies were assessed, ranging from prolonged treatment across 4 weeks to short-term treatment, also with delayed time-to-intervention. Cardiac function was assessed using echocardiography, including strain analysis. Impacts on the cardiac and systemic immune response were assessed using flow cytometry. CIRI-induced robust CD4+ biased T cell activation in the heart within 7 days. Treatment with abatacept significantly preserved key echocardiographic metrics of cardiac function. This treatment coincided with near-complete inhibition of the cardiac T cell response, as well as reductions in innate inflammatory cells. Collectively, this demonstrated a central mechanistic role for T cell activation post-MI with reperfusion. Evaluation of short-term intervention strategies further demonstrated sustained preservation of cardiac function even where treatment was delayed by 24 h. Mechanistically, our data indicate that over 50% of lost cardiac function post-MI with reperfusion is T cell dependent. CONCLUSION: T cell co-stimulation leading to activation is a central driver of the cardiac immune response following MI with reperfusion. The inhibition of this axis significantly protected against CIRI and preserved cardiac function. Ultimately, we highlight T cell immunomodulation and abatacept as highly promising approaches for clinical translation.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- CTLA-4-Ig therapy preserves cardiac function following myocardial infarction with reperfusion
- Date Crossref
- 01/10/2025
- Éditeur
- Oxford University Press (OUP)
- 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
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Baker Heart and Diabetes Institute Translational Cardiology Centre pays non établi dans la noticeOrganisation à but non lucratif
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The University of Melbourne Baker Department of Cardiometabolic Health pays non établi dans la noticeUniversité ou école supérieure
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Monash University pays non établi dans la noticeUniversité ou école supérieure
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The Alfred Hospital Department of Cardiology pays non établi dans la noticeÉtablissement de santé
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La Trobe University Bioimaging Platform pays non établi dans la noticeUniversité ou école supérieure
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Atherothrombosis and Vascular Biology Laboratory pays non établi dans la noticeStructure de recherche
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School of Translational Medicine Department of Immunology pays non établi dans la noticeUniversité ou école supérieure
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Molecular Imaging and Nanotherapeutics Laboratory pays non établi dans la noticeStructure de recherche
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Haematopoiesis and Leukocyte Biology Laboratory pays non établi dans la noticeStructure de recherche
Translational Cardiology Centre — Baker Heart and Diabetes Institute, Baker Department of Cardiometabolic Health — The University of Melbourne et Monash University, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.