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Canadian Journal of Cardiology

Sex-Dependent Mechanisms of Cell Death Modalities in Cardiovascular Disease

Published:September 21, 2022DOI:https://doi.org/10.1016/j.cjca.2022.09.015

      Abstract

      Despite currently available therapies, cardiovascular diseases (CVDs) are among the leading causes of death globally. Biological sex is a critical determinant of the occurrence, progression, and overall outcome of CVD. However, the underlying mechanisms are incompletely understood. A hallmark of CVD is cell death. Based on the inability of the human heart to regenerate, loss of functional cardiac tissue can lead to irreversible detrimental effects. Here, we summarize current knowledge on how biological sex affects cell death-related mechanisms in CVD. Initially, we discuss apoptosis and necrosis, but we specifically focus on the relatively newly recognized programmed necrosis-like processes: pyroptosis and necroptosis. We also discuss the role of 17β-estradiol (E2) in these processes, particularly in terms of inhibiting pyroptotic and necroptotic signalling. We put forward that a better understanding of the effects of biological sex and E2 might lead to the identification of novel targets with therapeutic potential.

      Résumé

      Malgré les traitements disponibles à l’heure actuelle, la maladie cardiovasculaire (MCV) figure parmi les principales causes de mortalité dans le monde. Le sexe biologique est un facteur déterminant important dans la survenue, la progression et l’issue globale de la MCV. Les mécanismes sous-jacents ne sont toutefois pas complètement élucidés. Une caractéristique de la MCV est la mort cellulaire. Comme le cœur humain est incapable de se régénérer, la perte de tissu cardiaque fonctionnel peut avoir des conséquences néfastes irréversibles. Nous résumons ici les connaissances actuelles sur le lien entre le sexe biologique et les mécanismes à l’origine de la mort cellulaire dans la MCV. Nous nous penchons d’abord sur l’apoptose et la nécrose, et nous nous attarderons ensuite sur deux processus de nécrose programmée reconnus depuis relativement peu de temps : la pyroptose et la nécroptose. Nous verrons également le rôle du 17β-estradiol (E2) dans ces processus, en particulier son effet inhibiteur sur la signalisation pyroptotique et nécroptotique. Nous faisons valoir qu’une meilleure compréhension des effets du sexe biologique et de l’E2 pourrait mener à l’identification de nouvelles cibles offrant un potentiel thérapeutique.
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