Cardiomyocyte Alpha-1A Adrenergic Receptors Mitigate Post-Infarct Remodeling and Mortality by Constraining Necroptosis

Clinical studies have shown that alpha 1-adrenergic receptor antagonists (alpha-blockers) are associated with increased heart failure risk. The mechanism underlying that hazard and whether it arises from direct inhibition of cardiomyocyte alpha 1-ARs or from systemic effects remain unclear. To address these issues, we created a mouse with cardiomyocyte-specific deletion of the alpha 1A-AR subtype and found that it experienced 70% mortality within 7 days of myocardial infarction driven, in part, by excessive activation of necroptosis. We also found that patients taking alpha-blockers at our center were at increased risk of death after myocardial infarction, providing clinical correlation for our translational animal models. (c) 2024 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).