Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction
| العنوان: | Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction |
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| المؤلفون: | Luca Danelli, Maxime Branchereau, Eric Camerer, Mathilde Lemitre, Nisa Renault, Béatrice Cousin, Pauline Marck, Adèle Richart, Elodie Luche, Pierre Launay, Sylvain M. Le Gall, Coralie L. Guerin, Jean-Sébastien Silvestre, Anta Ngkelo, Philippe Bonnin, Anaïs Kervadec, Jonathan A. Kirk, Hans Reimer Rodewald, Philippe Menasché, Mark J. Ranek, Patrick Bruneval, Christophe Heymes, José Vilar, Ulrich Blank, David A. Kass, Gregory Gautier, Louis Casteilla |
| المصدر: | The Journal of Experimental Medicine |
| بيانات النشر: | Rockefeller University Press, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Cardiac function curve, medicine.medical_specialty, CPA3, Carboxypeptidases A, Immunology, Myocardial Infarction, Tryptase, Sudden death, Article, Contractility, Mice, 03 medical and health sciences, Myofibrils, Internal medicine, medicine, Animals, Receptor, PAR-2, Immunology and Allergy, Calcium Signaling, Mast Cells, Myocardial infarction, Research Articles, Mice, Knockout, biology, Myocardium, medicine.disease, Cyclic AMP-Dependent Protein Kinases, Myocardial Contraction, Proto-Oncogene Proteins c-kit, 030104 developmental biology, Endocrinology, Heart failure, Proteolysis, cardiovascular system, biology.protein, Mast cell sarcoma, Calcium |
| الوصف: | Ngkelo et al. use a mast cell–deficient mouse model to reveal a protective role of mast cells in myocardial infarction, through regulation of the cardiac contractile machinery. Acute myocardial infarction (MI) is a severe ischemic disease responsible for heart failure and sudden death. Inflammatory cells orchestrate postischemic cardiac remodeling after MI. Studies using mice with defective mast/stem cell growth factor receptor c-Kit have suggested key roles for mast cells (MCs) in postischemic cardiac remodeling. Because c-Kit mutations affect multiple cell types of both immune and nonimmune origin, we addressed the impact of MCs on cardiac function after MI, using the c-Kit–independent MC-deficient (Cpa3Cre/+) mice. In response to MI, MC progenitors originated primarily from white adipose tissue, infiltrated the heart, and differentiated into mature MCs. MC deficiency led to reduced postischemic cardiac function and depressed cardiomyocyte contractility caused by myofilament Ca2+ desensitization. This effect correlated with increased protein kinase A (PKA) activity and hyperphosphorylation of its targets, troponin I and myosin-binding protein C. MC-specific tryptase was identified to regulate PKA activity in cardiomyocytes via protease-activated receptor 2 proteolysis. This work reveals a novel function for cardiac MCs modulating cardiomyocyte contractility via alteration of PKA-regulated force–Ca2+ interactions in response to MI. Identification of this MC-cardiomyocyte cross-talk provides new insights on the cellular and molecular mechanisms regulating the cardiac contractile machinery and a novel platform for therapeutically addressable regulators. |
| تدمد: | 1540-9538 0022-1007 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6abd60274d462c3d586932a63152ea16 https://doi.org/10.1084/jem.20160081 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....6abd60274d462c3d586932a63152ea16 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15409538 00221007 |
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