Estrogen-Mediated Protection in Myocardial Ischemia-Reperfusion Injury

Abstract

Before menopause, a woman has a relatively low risk for developing cardiovascular disease. After menopause, however, the risk increases nearly twofold and cardiovascular disease remains the number one cause of death among women. Observational trials and studies in animal models of cardiovascular disease suggested that females have reduced injury after myocardial ischemia and reperfusion injury. However, two large clinical trials, the women's health initiative (WHI) and the heart estrogen and progestin replacement study (HERS), found an increase in cardiovascular incidences in women taking hormone replacement therapy. The discrepancy between these data highlights the need for further research on the mechanism of estrogen in the cardiovascular system. Animal studies have demonstrated protective effects by endogenous estrogen (gender differences) and also by the administration of exogenous estrogen. In vivo studies suggest a possible anti-inflammatory mechanism of estrogen. Exogenous estrogen has been shown to have anti-oxidant activities. Pre-treatment with estrogen prior to myocardial ischemia and reperfusion causes a decrease in neutrophil infiltration into the irreversibly injured myocardium, decrease in C-reactive protein expression, and deposition of the membrane attack complex. This review will summarize the protection afforded by estrogen as well as discuss several possible mechanisms of protection for exogenous estrogen administration.

The Biochemical and histopathological effects of estrogen replacement therapy on the heart of ovariectomized female rats subjected to myocardial infarction

“…Our findings are also in accordance with those of previous studies that reported E2 to possess antioxidant activity because of its ability to bind to estrogen receptors and upregulate the expression of antioxidant enzymes through intracellular signaling pathways [9,[40][41][42][43].…”

Testosterone enhances estradiol's cardioprotection in ovariectomized rats

“…A number of clinical and experimental studies confirmed that estrogen has beneficial effects on the cardiovascular system, particularly in myocardial I/R injury, atherosclerosis, and arrhythmia (Booth & Lucchesi 2008). Xin et al (2002) found that estrogen plays a protective role in the hypertrophic response of the heart to Ca 2C dysregulation.…”

Mitochondrial Involvement in Cardiac Apoptosis During Ischemia and Reperfusion: Can We Close the Box?

“…Estrogens have been demonstrated to reduce the extent of irreversible myocardial injury, ventricular arrhythmias and infarct size after I/R [167]. Non-transcriptional actions of estrogens in myocardial I/R have been suggested to be due to stimulation of NO production, inhibition of myocardial calcium accumulation, preservation of mitochondrial structure and function and antioxidant action [168][169][170].…”

“…Non-transcriptional actions of estrogens in myocardial I/R have been suggested to be due to stimulation of NO production, inhibition of myocardial calcium accumulation, preservation of mitochondrial structure and function and antioxidant action [168][169][170]. Interestingly, estrogens improve not only female but also male cardiac function after I/R [167]. Estradiol hormone in mitochondria can act on membranes directly or indirectly through estrogen receptors that have been identified in mitochondria [171].…”