Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases

Abstract

This review summarizes recent evidence concerning hormonal and sex chromosome effects in obesity, atherosclerosis, aneurysms, ischemia/reperfusion injury, and hypertension. Cardiovascular diseases (CVD) occur and progress differently in the two sexes, because biological factors differing between the sexes have sex-specific protective and harmful effects. By comparing the two sexes directly, and breaking down sex into its component parts, one can discover sex-biasing protective mechanisms that might be targeted in the clinic. Gonadal hormones, especially estrogens and androgens, have long been found to account for some sex differences in CVD, and molecular mechanisms mediating these effects have recently been elucidated. More recently the inherent sexual inequalities in effects of sex chromosome genes have also been implicated as contributors in animal models of CVDs, especially a deleterious effect of the second X chromosome found in females but not in males. Hormonal and sex chromosome mechanisms interact in the sex-specific control of certain diseases, sometimes by opposing the action of the other.

Targetable cellular signaling events mediate vascular pathology in vascular Ehlers-Danlos syndrome

“…In this light, androgen signaling may play a broader role in aortic aneurysm and dissection, but the exact mechanism still needs to be elucidated. Prior experience in experimentally induced aneurysm in rodents has suggested that androgen signaling can exacerbate aortic wall inflammation, but little is known about the precise mechanism (51,(53)(54)(55)(56)(57)(58)(59). It is notable that in our mouse model of vEDS, the androgen-dependent risk seen at puberty was not associated with overt inflammation.…”

A Novel and Simply Calculated Cardiac Load Index Correlates With Coronary Artery Disease

“…Risk factors for CAD differ between males and females due to differences in the genes carried by the X and Y chromosomes and in the sex hormones. [20,21]. Women display greater cardiac strength values than men, but male myocardia bers are more sensitive to calcium than are female bers [22].…”

Sex difference between target levels of cholesterol-related parameters and post-PCI long-term clinical outcomes: From the FU-Registry

“…The influence of female menopause, and particularly of the hormone estrogen, is considered to be a main cause of such sex differences in plasma lipid parameter levels. Estrogen has been reported to have various protective actions on cardiac vessels [17,18]. It is generally accepted that this antiarter-iosclerotic action of endogenous estrogen can explain why the incidence of CAD is lower in premenopausal females than in males [19].…”