Sex-specific and hormone-related differences in vascular remodeling in atherosclerosis.

Atherosclerosis, a lipid-driven inflammatory disease, is the main underlying cause of cardiovascular diseases (CVDs) both in men and women. Sex-related dimorphisms regarding CVDs and atherosclerosis were observed since more than a decade ago. Inflammatory mediators such as cytokines, but also endothelial dysfunction, vascular smooth muscle cell migration and proliferation lead to vascular remodeling but are differentially affected by sex. Each year a greater number of men die of CVDs compared to women and are also affected by CVDs at an earlier age (40-70 years old) while women develop atherosclerosis-related complications mainly after the menopause (60+ years). The exact biological reasons behind this discrepancy are still not well understood. From the numerous animal studies on atherosclerosis, only a few include both sexes and even less investigate and highlight the sex-specific differences that may arise. Endogenous sex hormones such as testosterone and estrogen modulate the atherosclerotic plaque composition as well as the frequency of such plaques. In men, testosterone seems to act like a double-edged sword as its decrease with aging correlates with an increased risk of atherosclerotic CVDs, while testosterone is also reported to promote inflammatory immune cell recruitment into the atherosclerotic plaque. In premenopausal women estrogen exerts anti-atherosclerotic effects, which decline together with its level after menopause resulting in increased CVD risk in aging women. However, the interplay of sex hormones, sex-specific immune responses and other sex-related factors is still incompletely understood. This review highlights reported sex-differences in atherosclerotic vascular remodeling and the role of endogenous sex-hormones in this process.