Sex differences in endothelial function important to vascular health and overall cardiovascular disease risk across the lifespan

Abstract

Diseases of the cardiovascular system are the leading cause of morbidity and mortality in men and women in developed countries, and CVD is becoming more prevalent in developing countries. Atherosclerotic cardiovascular disease (CVD) prevalence in men is greater than in women until menopause, when the prevalence of CVD increases in women until it exceeds that of men. Endothelial function is a barometer of vascular health and a predictor of atherosclerosis that may provide insights into sex differences in CVD, as well as how and why CVD risk drastically changes with menopause. Studies of sex differences in endothelial function are conflicting, with some studies showing earlier decrements in endothelial function in men compared to women, while others showing similar age-related declines between the sexes. Because the increase in CVD risk coincides with menopause, it is generally thought that female hormones, in particular estrogens, are cardioprotective. Further, it is often proposed that androgens are detrimental. In truth, the relationships are more complex. This review will first address female and male sex hormones and their receptors, and how these interact with the cardiovascular system, particularly the endothelium, in healthy young women and men. Second, we will address sex differences in sex steroid receptor-independent mechanisms controlling endothelial function, focusing on the vascular endothelin and the renin-angiotensin systems, in healthy young women and men. Finally, we will discuss sex differences in age-associated endothelial dysfunction, focusing on the role of attenuated circulating sex-hormones in these effects.

Citrulline supplementation improves spatial memory in a murine model for Alzheimer’s disease

“…Finally, we found a significant increase in NO of female transgenic mice compared to their male counterparts. In this regard, it is known that sex hormones influence endothelial function through their effects on agonists and contribute to key functional differences between males and females related to endothelial function and cardiovascular disease risk [44]. It is known that estrogen binding to activated eNOS promotes the production of NO [45] in the endothelial caveola [46] which could affect cognition.…”

Mechanisms underlying the influence of oestrogen on cardiovascular physiology in women

“…How female and male sex hormones interact with the cardiovascular system, and in age‐associated endothelial dysfunction in healthy woman and men has been recently reviewed in depth (Stanhewicz et al . ).…”

“…Thus, not only does oestradiol decline with ageing, ERα receptor expression also declines, and an increase in oxidative stress is produced as well. How female and male sex hormones interact with the cardiovascular system, and in age-associated endothelial dysfunction in healthy woman and men has been recently reviewed in depth (Stanhewicz et al 2018).…”

“…In this regard, the blockade of Mas receptor is equivalent to ER blockade in preventing the effects of oestradiol, indicating crosstalk between oestradiol and the Ang-(1-7)-Mas axis (Sobrino et al 2017). Thus, the loss of cardiovascular protection observed in postmenopausal women could also partly result from the change from the ACE2-RAS protective axis to the classic ACE-RAS pathway (Komukai et al 2010;Hilliard et al 2013b;Stanhewicz et al 2018).…”

Novel Insights into the Mode of Action of Vasorelaxant Synthetic Polyoxygenated Chalcones

“…Interestingly, epidemiological studies indicate that the prevalence of CVDs is lower in premenopausal women compared to age-matched men and significantly increases in women after menopause, suggesting a protective role of estrogens in premenopausal women [4,5]. Both estrogen receptor α (ERα) and estrogen receptor β (ERβ) are involved in cardiovascular protection with a predominant role of ERα at the vascular level [6,7].…”