Mechanistic Pathways of Sex Differences in Cardiovascular Disease
Reads0
Chats0
TLDR
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.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.read more
Citations
More filters
Journal ArticleDOI
Sex and gender: modifiers of health, disease, and medicine.
Franck Mauvais-Jarvis,Noel Bairey Merz,Peter J. Barnes,Roberta Diaz Brinton,Juan Jesus Carrero,Dawn L. DeMeo,Geert J. De Vries,C. Neill Epperson,Ramaswamy Govindan,Sabra L. Klein,Amedeo Lonardo,Pauline M. Maki,Louise D. McCullough,Vera Regitz-Zagrosek,Vera Regitz-Zagrosek,Judith G. Regensteiner,Joshua B. Rubin,Kathryn Sandberg,Ayako Suzuki,Ayako Suzuki +19 more
TL;DR: Clinicians and researchers are guided to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.
Journal ArticleDOI
Estrogens in Male Physiology.
Paul S. Cooke,Paul S. Cooke,Paul S. Cooke,Manjunatha K. Nanjappa,Manjunatha K. Nanjappa,Manjunatha K. Nanjappa,CheMyong Ko,CheMyong Ko,CheMyong Ko,Gail S. Prins,Gail S. Prins,Gail S. Prins,Rex A. Hess,Rex A. Hess,Rex A. Hess +14 more
TL;DR: Estrogens are important physiological regulators in males, and future studies may reveal additional roles for estrogen signaling in various target tissues.
Journal ArticleDOI
Sex differences in pharmacokinetics predict adverse drug reactions in women
TL;DR: Sex differences in pharmacokinetics strongly predict sex-specific ADRs for women but not men, and the absence of sex-stratified PK information in public records for hundreds of drugs raises the concern that sex differences in PK values are widespread and of clinical significance.
Journal ArticleDOI
Gut microbiota and cardiovascular disease: opportunities and challenges
TL;DR: An interdisciplinary approach is required to shed light on gut bacterial-mediated mechanisms to enable efficacious and high-precision preventative and therapeutic strategies for CAD.
Journal ArticleDOI
Higher mortality of COVID-19 in males: sex differences in immune response and cardiovascular comorbidities.
TL;DR: It is demonstrated that biological sex is a fundamental variable of critical relevance to the authors' mechanistic understanding of SARS-CoV-2 infection and the pursuit of effective COVID-19 preventative and therapeutic strategies.
References
More filters
Journal ArticleDOI
The steroid and thyroid hormone receptor superfamily
TL;DR: A superfamily of regulatory proteins that include receptors for thyroid hormone and the vertebrate morphogen retinoic acid is identified, suggesting mechanisms underlying morphogenesis and homeostasis may be more ubiquitous than previously expected.
Journal ArticleDOI
Third universal definition of myocardial infarction
Kristian Thygesen,Joseph S. Alpert,Allan S. Jaffe,Maarten L. Simoons,Bernard R. Chaitman,Harvey D. White +5 more
TL;DR: Information on MI rates can provide useful information regarding the burden of CAD within and across populations, especially if standardized data are collected in a manner that …
Journal ArticleDOI
Cloning of a novel receptor expressed in rat prostate and ovary.
TL;DR: It is concluded that clone 29 cDNA encodes a novel rat ER, which is suggested be named rat ERbeta to distinguish it from the previously cloned ER (ERalpha) from rat uterus.
Journal ArticleDOI
Impact of Atrial Fibrillation on the Risk of Death The Framingham Heart Study
Emelia J. Benjamin,Philip A. Wolf,Ralph B. D'Agostino,Halit Silbershatz,William B. Kannel,Daniel Levy +5 more
TL;DR: There was a significant AF-sex interaction: AF diminished the female advantage in survival and AF remained significantly associated with excess mortality, with about a doubling of mortality in both sexes in subjects free of valvular heart disease and preexisting cardiovascular disease.
Journal ArticleDOI
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
David E. Harrison,Randy Strong,Zelton D Sharp,James F. Nelson,Clinton M. Astle,Kevin Flurkey,Nancy L. Nadon,J. Erby Wilkinson,Krystyna Frenkel,Christy S. Carter,Christy S. Carter,Marco Pahor,Marco Pahor,Martin A. Javors,Elizabeth Fernandez,Richard A. Miller +15 more
TL;DR: It is reported that rapamycin, an inhibitor of the mTOR pathway, extends median and maximal lifespan of both male and female mice when fed beginning at 600 days of age.