Title:Selective Activation of G Protein-coupled Estrogen Receptor 1
Attenuates Atherosclerosis
Volume: 31
Issue: 27
Author(s): Mohammad Zulqurnain Haider, Amirhossein Sahebkar and Ali H. Eid*
Affiliation:
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, P.O. Box 2713,
Doha, Qatar
Keywords:
Estrogen, cardiovascular disease, atherosclerosis, GPER1, estrogen receptors, PCSK9, LDL.
Abstract: Atherosclerosis remains a leading contributor to cardiovascular disease-associated
morbidity and mortality. Interestingly, atherosclerosis-associated mortality rate is
higher in men than women. This suggested a protective role for estrogen in the cardiovasculature.
These effects of estrogen were initially thought to be mediated by the classic estrogen
receptors, ER alpha, and beta. However, genetic knockdown of these receptors did
not abolish estrogen’s vasculoprotective effects suggesting that the other membranous Gprotein
coupled estrogen receptor, GPER1, maybe the actual mediator. Indeed, in addition
to its role in vasotone regulation, this GPER1 appears to play important roles in regulating
vascular smooth cell phenotype, a critical player in the onset of atherosclerosis.
Moreover, GPER1-selective agonists appear to reduce LDL levels by promoting the expression
of LDL receptors as well as potentiating LDL re-uptake in liver cells. Further
evidence also show that GPER1 can downregulate Proprotein Convertase Subtilisin/
Kexin type 9, leading to suppression of LDL receptor breakdown. Here, we review
how selective activation of GPER1 might prevent or suppress atherosclerosis, with less
side effects than those of the non-selective estrogen.
