ESR1 in myocardial infarction

Abstract

Women live longer than men; this can be attributed in part to the function of estrogens. In premenopausal women 17β-estradiol (E2) is produced mainly by the ovaries. Extra-ovarian sources of this hormone comprise adipose tissue, breast tissue, bone, leukocytes, heart, testes, prostate, adrenal tissues, and some brain structures. E2 exerts the majority of its biological functions by interacting with the nuclear receptors ERα and ERβ, encoded by the ESR1 and ESR2 genes, respectively. The genomic mechanism of ER action is the regulation of the activity of target genes. In addition, E2 induces rapid cellular effects in transcription-independent, non-genomic mechanisms, acting via receptors localized in the plasma membrane, in the cytoplasm, and in the mitochondria. Notably, ERα commonly serves as an extra-nuclear receptor of E2. In wild type animal models of cardiac ischemia ERα activation reduces infarct size, apoptosis of cardiomyocytes, inflammation, and oxidative stress, induces vasodilatation and increases neovascularization. The cardioprotective role of ERα in human is not fully elucidated. An individual with disruptive ESR1 mutation had dysfunctional epithelium and suffered from early cardiovascular disease. An association of the common ESR1 -397T>C and -351A>G polymorphisms and of other polymorphisms with cardiovascular disease and with myocardial infarction is still not firmly established.