Affiliation:
1. Institute of Gender in Medicine & Center for Cardiovascular Research, Charite University Hospital, and DZHK (German Centre for Cardiovascular Research), Berlin, Germany
Abstract
Major differences between men and women exist in epidemiology, manifestation, pathophysiology, treatment, and outcome of cardiovascular diseases (CVD), such as coronary artery disease, pressure overload, hypertension, cardiomyopathy, and heart failure. Corresponding sex differences have been studied in a number of animal models, and mechanistic investigations have been undertaken to analyze the observed sex differences. We summarize the biological mechanisms of sex differences in CVD focusing on three main areas, i.e., genetic mechanisms, epigenetic mechanisms, as well as sex hormones and their receptors. We discuss relevant subtypes of sex hormone receptors, as well as genomic and nongenomic, activational and organizational effects of sex hormones. We describe the interaction of sex hormones with intracellular signaling relevant for cardiovascular cells and the cardiovascular system. Sex, sex hormones, and their receptors may affect a number of cellular processes by their synergistic action on multiple targets. We discuss in detail sex differences in organelle function and in biological processes. We conclude that there is a need for a more detailed understanding of sex differences and their underlying mechanisms, which holds the potential to design new drugs that target sex-specific cardiovascular mechanisms and affect phenotypes. The comparison of both sexes may lead to the identification of protective or maladaptive mechanisms in one sex that could serve as a novel therapeutic target in one sex or in both.
Funder
German Centre for Cardiovascular Research (DZHK)
German Research Foundation (DFG)
German Federal Ministry of Education and Research (BMBF)
European Union
Margarete Ammon Foundation
Publisher
American Physiological Society
Subject
Physiology (medical),Molecular Biology,Physiology,General Medicine
Cited by
430 articles.
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