Abstract
Cardiovascular disease (CVD) is the biggest cause of sickness and mortality worldwide in both males and females. Clinical statistics demonstrate clear sex differences in risk, prevalence, mortality rates, and response to treatment for different entities of CVD. The reason for this remains poorly understood. Non-coding RNAs (ncRNAs) are emerging as key mediators and biomarkers of CVD. Similarly, current knowledge on differential regulation, expression, and pathology-associated function of ncRNAs between sexes is minimal. Here, we provide a state-of-the-art overview of what is known on sex differences in ncRNA research in CVD as well as discussing the contributing biological factors to this sex dimorphism including genetic and epigenetic factors and sex hormone regulation of transcription. We then focus on the experimental models of CVD and their use in translational ncRNA research in the cardiovascular field. In particular, we want to highlight the importance of considering sex of the cellular and pre-clinical models in clinical studies in ncRNA research and to carefully consider the appropriate experimental models most applicable to human patient populations. Moreover, we aim to identify sex-specific targets for treatment and diagnosis for the biggest socioeconomic health problem globally.
Highlights
Cardiovascular disease (CVD) is the leading cause of death in females worldwide
While clear sex differences are documented in human disease, relatively few studies have focused on searching for sex differences in ncRNA responses in human [69] (Table 1)
In CVD, FCG mouse model has been used for instance to demonstrate the relationship of ischemic stroke sensitive with gonadal hormones rather than sex chromosomal component and proving that stroke outcomes worsen in XX genotype compared to XY chromosomes [171]
Summary
Cardiovascular disease (CVD) is the leading cause of death in females worldwide. Despite this, females are under-represented in clinical trials as well as pre-clinical investigations being the analysis. While males and females share most of the traditional cardiovascular risk factors, their impact on health differs in a sex-specific manner. There are cardiovascular risk factors, their impact on health differs in a sex-specific manner. The risk of developing different entities of CVD shows a sex-related distribution. Equal participation and sex-specific and cells are biologically different. Recommendations relating to the inclusion of females in research have been extended beyond beyond clinical research to include cells and animal models [6]. Approaching translational research with sex differences in mind is needed for comprehensive comprehensive understanding of the sexual dimorphism, which may lead to the improvement of understanding of the by sexual dimorphism, which diagnostic may lead toand thetherapeutic improvement of clinicalHere, outcome clinical outcome developing sex-specific guidelines. Schroen and presents aspectsin ofrisk, the discussion ofsensitivity this important topic area. and effectivity of Withthis sexreview differences emerging prevalence, of biomarkers, treatment options, it formed one of the main topics of the EU-CardioRNA COST Action 3rd working
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