About this Research Topic
Cardiovascular disease (CVD) describes disorders of the heart and blood vessels and is the greatest cause of mortality and morbidity worldwide, representing a major socioeconomic burden. Epidemiology and clinical studies demonstrate clear sex differences for CVD risk, prevalence, prognosis and response to treatment. Despite this, females are under-represented in clinical trials and pre-clinical investigations. Cardiovascular disease is driven by core transcriptional, biochemical and structural changes in the heart and vasculature. Sex hormones can directly influence gene transcription, both directly in target genes with estrogen and androgen receptor binding sites in promoter regions, as well as indirectly influencing epigenetic modifications. Epigenetics describes DNA and histone modifications that do not alter the DNA sequence as well as RNA-based mechanisms that regulate gene expression. A number of epigenetic modifiers are encoded on sex chromosomes (X and Y). Moreover, a limited number of studies has shown X chromosome reactivation in females in disease and aging. Not only can this cause further changes in epigenetics through a trans mechanism, on other chromosomes, but further causes sex dimorphism in the transcriptional landscape and cardiovascular function. In this manner, sex-dependent genetic and epigenetic mechanisms define pathophysiological processes in CVD. Differential genetic and epigenetic factors are thought to underlie sex differences in CVD. Yet, in a systematic review of translational cardiovascular epigenetic studies, 86 % of reported studies used solely male animals or human subjects (Hartman et al., 2018). In our Research Topic, we look forward to building a collection of articles addressing genetics and gene regulatory mechanisms underlying sex differences in CVD. Subjects covered will include, but not limited to: - X-chromosome reactivation - Sex hormone-driven transcriptional changes in the CV system - Estrogen and androgen receptor regulation of gene expression - Epigenetics and the menopause - Sex differences in RNA biomarkers for CVD - Experimental models and sex differences in CVD research - Sex-specific mechanisms of CVD risk factors
Keywords: sex, sex hormones, epigenetics, estrogen, androgen
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