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World J Cardiol. Jun 26, 2014; 6(6): 367-375
Published online Jun 26, 2014. doi: 10.4330/wjc.v6.i6.367
G-protein-coupled estrogen receptor as a new therapeutic target for treating coronary artery disease
Guichun Han, Richard E White
Guichun Han, Women’s Health Division, Michael E DeBakey Institute, Department of Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A and M University, College Station, TX 77843, United States
Richard E White, Department of Biomedical Sciences, Georgia Campus-Philadelphia College of Osteopathic Medicine, Suwanee, GA 30024, United States
Author contributions: Han G and White RE contributed equally to this paper; all authors have approved the final review of this paper.
Supported by The American Heart Association, Texas Affiliate, No. 7370061; and the Center for Chronic Disorders of Aging, PCOM
Correspondence to: Guichun Han, MD, PhD, Women’s Health Division, Michael E DeBakey Institute, Department of Physiology and Pharmacology, College of Veterinary Medicine and Biomedical Sciences, Texas A and M University, MS 4466, College Station, TX 77843, United States. ghan@cvm.tamu.edu
Telephone: +1-979-8456099 Fax: +1-979-8456544
Received: December 28, 2013
Revised: March 6, 2014
Accepted: April 25, 2014
Published online: June 26, 2014
Abstract

Coronary heart disease (CHD) continues to be the greatest mortality risk factor in the developed world. Estrogens are recognized to have great therapeutic potential to treat CHD and other cardiovascular diseases; however, a significant array of potentially debilitating side effects continues to limit their use. Moreover, recent clinical trials have indicated that long-term postmenopausal estrogen therapy may actually be detrimental to cardiovascular health. An exciting new development is the finding that the more recently discovered G-protein-coupled estrogen receptor (GPER) is expressed in coronary arteries-both in coronary endothelium and in smooth muscle within the vascular wall. Accumulating evidence indicates that GPER activation dilates coronary arteries and can also inhibit the proliferation and migration of coronary smooth muscle cells. Thus, selective GPER activation has the potential to increase coronary blood flow and possibly limit the debilitating consequences of coronary atherosclerotic disease. This review will highlight what is currently known regarding the impact of GPER activation on coronary arteries and the potential signaling mechanisms stimulated by GPER agonists in these vessels. A thorough understanding of GPER function in coronary arteries may promote the development of new therapies that would help alleviate CHD, while limiting the potentially dangerous side effects of estrogen therapy.

Keywords: G-protein-coupled estrogen receptor, Coronary arteries, G-1, Atherosclerosis, Estrogen

Core tip: A continuing controversy in cardiology is the impact of estrogen on coronary arteries. This review provides the latest information on the discovery of a novel estrogen receptor in these vessels: the G-protein-coupled estrogen receptor (GPER). Recent findings demonstrate that GPER activation induces coronary artery relaxation and attenuates the proliferation and migration of coronary smooth muscle cells. Thus, GPER appears to be a promising, novel pharmacological target that could increase coronary blood flow in diseased arteries and prevent or reverse the progression of coronary atherosclerotic disease, and do so with potentially fewer dangerous side effects associated with traditional estrogen therapy.