Estrogen, Aging and the Cardiovascular System

Abstract

Estrogen is a powerful hormone with pleiotropic effects. Estrogens have potent antioxidant effects and are able to reduce inflammation, induce vasorelaxation and alter gene expression in both the vasculature and the heart. Estrogen treatment of cultured cardiac myocytes and endothelial cells rapidly activates NFκB, induces heat-shock protein (HSP)-72, a potent intracellular protective protein, and protects cells from simulated ischemia. In in vivo models, estrogens protect against ischemia and trauma/hemorrhage. Estrogens may decrease the expression of soluble epoxide hydrolase, which has deleterious effects on the cardiovascular system through metabolism of epoxyeicosatrienoic acids. Natural (endogenous) estrogens in premenopausal women appear to protect against cardiovascular disease and yet controlled clinical trials have not indicated a benefit from estrogen replacement postmenopause. Much remains to be understood in regards to the many properties of this powerful hormone and how changes in this hormone interact with aging-associated changes. The unexpected negative results of trials of estrogen replacement postmenopause probably arise from our lack of understanding of the many effects of this hormone.

Antioxidant effect of estrogen on bovine aortic endothelial cells

“…Stice et al asserted that estrogen played roles on protection cardiovascular system from ischemia by activating NFB, inducing heat-shock protein (hsp)-72 and decreasing the expression of soluble epoxide hydrolase [53]. Estradiol also reported to promote the association of hsp-90 with endothelial nitric oxide synthase and reduce the Ca2+ requirement for its activation [54].…”

Sex Differences in Lifespan

“…The increasing realization that early life events can have manifold later life health impacts make the examination of early life hormonal profiles of particular interest (Bartke et al, 2016; Brakefield et al, 2005; Sonntag et al, 2005). Assuming that the survival advantage is fairly general to female mammals (something that is still unknown), then the anti-oxidant (Mann et al, 2007; Stice et al, 2009) and anti-inflammatory (Benedusi et al, 2012; Villa et al, 2015) properties of estrogen seem like one obvious place to look for an explanation. Both oxidative damage and chronic low-grade inflammatory activation in later life have been implicated in aging (Barja, 2004; Finch, 2007; Ku and Sohal, 1993).…”

Brain sex matters: Estrogen in cognition and Alzheimer’s disease

“…In addition to the well-established functions of estrogens in female reproduction, studies demonstrated significant non-reproductive functions of estrogens in the regulation of lipid and carbohydrate metabolism, skeletal homeostasis, the cardiovascular system, and the central nervous system (CNS) in both males and females [23; 24; 25; 26; 27; 28; 29]. …”