Aging is associated with abnormalities of vascular function, with the cardiovascular system of men and women affected differently. The development of coronary heart disease (CHD), atherosclerosis and endothelial dysfunction in women lags behind that of age-matched men, until the onset of menopause. Estrogens are implicated in the protective effects of gender in the regulation of blood pressure and vascular function, with the increased incidence of CHD after menopause largely attributed to estrogen deficiency. As long-term hormone replacement therapy (HRT) is associated with an increased risk of breast cancer and stroke, research has focused on the cardiovascular benefits of alternative strategies, including selective estrogen receptor modulators and plant-derived phytoestrogens, such as the isoflavones genistein, daidzein and its metabolite equol. The interest in soy isoflavones is based on the lower incidence of CHD in populations consuming soy rich foods (see reviews: Siow et al., Free Radic Biol Med 2007;42:909-925; Mann et al., Cardiovasc Res, 2007 in press). Dietary isoflavones are likely to protect against cardiovascular disease via the activation of intracellular signalling pathways leading to increased NO generation and bioavailability and enhanced transcriptional activation of antioxidant genes. Our studies in aged male Sprague-Dawley rats suggest that protection against CHD by a soy isoflavone enriched diet may be due to increased expression/activity endothelial nitric oxide synthase (eNOS) and other key antioxidant defence genes (Mahn et al., FASEB J, 2005;19:1755-1757). Moreover, improvements in flow-mediated dilatation have been reported in postmenopausal women receiving isoflavone supplementation (Squadrito et al., Am J Med 2003; 114:470-476). The role of isoflavones in modulating NO and ROS production in vascular cells and the implications of aging will be reviewed.

Supported by British Heart Foundation, Heart Research UK and BBSRC