Estrogen receptor activation and cardioprotection in ischemia reperfusion injury.
Premenopausal females have a comparably lower incidence of cardiovascular disease than their male counterparts. Although estrogen and activation of estrogen receptors (ERs) have been found to contribute to female protection, the complex mechanisms involved are unclear. Besides altering gene transcription, estrogen could elicit its cardioprotective effect via ER-mediated nongenomic signaling pathways. In addition to the two classic nuclear ER isoforms, ERα and ERβ, a G-protein coupled ER (GPR30 or GPER) has been found to be expressed in cardiomyocytes and plays an acute cardioprotective role in ischemia reperfusion injury. By using isoform-specific ER knockout mouse models and/or their specific modulators, the mechanisms of the different ERs involved in cardioprotection have been explored. In this review, we will focus on the signaling pathways leading to cardioprotection in ischemia reperfusion injury after ER activation and discuss the possibility and promise of specific ER modulators to treat ischemic heart diseases.
National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Anne M
AM
Deschamps
Elizabeth
E
Murphy
Junhui
J
Sun
D000818:Animals; D002317:Cardiovascular Agents / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects
D002317:Cardiovascular Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020845:Selective Estrogen Receptor Modulators