Unravelling the cardioprotective mechanism of action of estrogens

Extract

See article by Xu et al.[1](pages 836–844) in this issue.

Cardiovascular diseases are the major cause of morbidity and mortality in the developed world, and are increasing in significance in the developing world. Elucidation of the mechanisms involved in preventing the development of coronary artery disease and protecting the myocardium against the deleterious consequences of myocardial ischaemia therefore stays an important research goal. The sex hormone estrogen has received increased attention for its ability to exert cardioprotective effects against atherosclerosis, but it has become clear that estrogen also exerts a direct protective effect against ischaemia/reperfusion injury on the myocardium. In this edition of Cardiovascular Research Xu et al. [1] provide evidence for decreased TNFα production during ischaemia/reperfusion in the mechanism of estrogen-mediated cardiac protection.

There is an abundance of scientific evidence for the protective effect of estrogen against atherosclerosis, such as short-term vasodilating effects as well as long-term vascular protective and anti-atherosclerotic effects [2]. Epidemiological evidence shows that pre-menopausal women have a reduced risk for mortality from cardiovascular diseases [3] and that women are at a lower risk for the development of heart failure [4] and have enhanced cognitive function and reduced neurodegeneration associated with Alzheimer's disease and stroke [5]. Further proof for the protective effect of female gender is the fact that post-menopausal women have a similar or even increased risk for cardiovascular disease compared to men [3] and have an increased risk for adverse outcome after myocardial infarction and acute coronary syndromes, despite similar treatment with thrombolysis and percutaneous interventions [6]. It was therefore postulated that estrogen replacement would be beneficial in preventing cardiovascular diseases in post-menopausal females. However, clinical trials designed to investigate the effects of estrogen replacement therapy in secondary prevention were surprising–in the Heart and Estrogen/Progestin Replacement Study (HERS) no overall cardiovascular benefit was found, and in fact an increase in coronary heart disease during the first year was observed [7]. In the Women's Health Initiative (WHI) study estrogen/progestin replacement was stopped because an increased cardiovascular risk occurred [8]. This does not invalidate the significance of estrogen for cardiovascular protection, but probably tells us that we still have to elucidate the exact pharmacological means of attaining benefit for our patients.