Abstract
Heart disease in women remains underappreciated, underdiagnosed and undertreated. Further, although we are starting to understand some of the social and behavioral determinants for this, the biological basis for the increased rate of rise in atherosclerosis risk in women after menopause remains very poorly understand. In this review we will outline the scope of the clinical issues related to heart disease in women, the emerging findings regarding the biological basis underlying the increased prevalence of atherosclerotic risk factors in postmenopausal women (vs. men) and the role of the G protein-coupled estrogen receptor (GPER) and its genetic regulation as a determinant of these sex-specific risks. GPER is a recently appreciated GPCR that mediates the rapid effects of estrogen and aldosterone. Recent studies have identified that GPER activation regulates both blood pressure. We have shown that regulation of GPER function via expression of a hypofunctional GPER genetic variant is an important determinant of blood pressure and risk of hypertension in women. Further, our most recent studies have identified that GPER activation is an important regulator of low density lipoprotein (LDL) receptor metabolism and that expression of the hypofunctional GPER genetic variant is an important contributor to the development of hypercholesterolemia in women. GPER appears to be an important determinant of the two major risk factors for coronary artery disease-blood pressure and LDL cholesterol. Further, the importance of this mechanism appears to be greater in women. Thus, the appreciation of the role of GPER function as a determinant of the progression of atherosclerotic disease may be important both in our understanding of cardiometabolic function but also in opening the way to greater appreciation of the sex-specific regulation of atherosclerotic risk factors.
Highlights
The risk of heart disease in women remains underappreciated despite concerted efforts by a range of health care agencies and non-governmental organizations
Much of what we know about the biological basis for the actions of estrogens is based on the activation of classic estrogen receptors (ER) [11]
Having demonstrated that this genetic variant of G protein-coupled estrogen receptor (GPER) was hypofunctional we further examined whether the expected decrease in GPER vascular functionality in those carrying this polymorphism translated into an altered cardiovascular phenotype
Summary
The risk of heart disease in women remains underappreciated despite concerted efforts by a range of health care agencies and non-governmental organizations. We know that (i) women (after menopause) have a faster rise in cardiovascular (CV) risk than men (ii) that women with risk factors for heart disease are less likely to be treated appropriately (iii) that women with heart disease are less likely to be diagnosed, less likely to be treated and more likely to die of their heart disease or of complications of revascularization (reviewed in [1]) Despite these inconvenient truths, the biological basis for sex-specific risks of heart disease in women remains unclear. Important biological differences in heart disease determinants between sexes are beginning to be appreciated These include differences in clotting characteristics and differences in the presentation of atherosclerosis (towards smaller vessel disease presentation in women) [5]. The basis of these genetic differences (beyond the absence or presence of a Y chromosome) has remained largely unstudied
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
