Estrogens and atherosclerosis: insights from animal models and cell systems

Abstract

Estrogens not only play a pivotal role in sexual development but are also involved in several physiological processes in various tissues including vasculature. While several epidemiological studies documented an inverse relationship between plasma estrogen levels and the incidence of cardiovascular disease and related it to the inhibition of atherosclerosis, an interventional trial showed an increase in cardiovascular events among postmenopausal women on estrogen treatment. The development of atherosclerotic lesions involves complex interplay between various pro-or anti-atherogenic processes that can be effectively studied only in vivo in appropriate animal models. With the advent of genetic engineering, transgenic mouse models of atherosclerosis have supplemented classical dietary cholesterolinduced disease models such as the cholesterol-fed rabbit. In the last two decades, these models were widely applied along with in vitro cell systems to specifically investigate the influence of estrogens on the development of early and advanced atherosclerotic lesions. The present review summarizes the results of these studies and assesses their contribution toward better understanding of molecular mechanisms underlying anti-and/or pro-atherogenic effects of estrogens in humans.

17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway

“…Previous research has focused on the anti-proliferative and anti-migratory properties of estrogen on VSMCs (29). Here, we elucidated a novel atheroprotective effect of estrogen that E2 promotes cholesterol efflux from VSMCs and suppresses VSMC-derived foam cell formation.…”

“…Pre-incubation with ICI 182,780 to antagonize ERs blocked the E2-mediated upregulation of LXRα, ABCA1 and ABCG1 expression and attenuation of cholesteryl ester accumulation in VSMCs, indicating ER dependence. There are two different isforms of ERs, ERα and ERβ, which are expressed in endothelial cells, VSMCs and macrophages (29). Previous research found that ERα may be the major mediator of the atheroprotective effects of estrogen (40).…”

Testosterone, dihydrotestosterone and estradiol are differentially associated with carotid intima-media thickness and the presence of carotid plaque in men with and without coronary artery disease

“…The Tromsø cohort was derived from community-dwelling men with a prevalence of CVD that was slightly higher than our community-dwelling group (17.5% vs 9.6%) [11]. The SHIP cohort was derived from a population characterised by a relatively high prevalence of cardiovascular risk factors, although the proportion of men with tor subtypes and cellular targets [37]. Therefore, further studies are needed to clarify whether E2 differentially modulates cardiovascular risk in men with either early or more advanced degrees of atherosclerosis.…”

The molecular and genetic aspects of adolescent girls anomalous uterine bleeding: the role of endothelial dysfunction syndrome

“…Tissue hypoxia can trigger the anomalous angiogenesis by vascular cells which are increasing the vascular endothelial growth factor (VEGF) synthesis. It was also shown that the hypoxia decreases the endometrial blood flow and increases the production of oxygen active forms at endothelial dysfunction syndrome [27,28]. This process can also increase the VEGF and angiopoetin-2 (Ang-2) synthesis in endometrial endothelial cells [11,29].…”