The proposal is aimed at continuing to investigate the theory that estrogen (E2) is involved in protection against atherosclerosis. Epidemiological studies have supported the fact that E2 replacement provides a protective effect against coronary disease. After menopause the risk of myocardial Infarction increases and the incidence approaches equal to that of males after the age of 55, E2 replacement results in a 50% reduction in cardiovascular and cerebrovascular mortality relative to women who do not receive therapy. The hypothesis is that E2 via the endothelial cell(EC) E2 receptor(ER) is effecting EC function resulting in inhibition of cytokine-mediated endothelial cell adhesion molecules(CAM) thereby decreasing the adhesive state of the endothelium in inflammation; augmentation of basal nitric oxide synthase (NOS) activity which results in vasomotor stability enhancement and inhibition of leukocyte adhesion to the endothelium. Based on preliminary data further studies will be elucidating the cis-acting elements in the CAM promotors which E2 interacts using a transfection model; determining if E2 regulation of genes for CAM is by interaction of the ER complex with nuclear E2 response elements or by regulation of other gene products; studying the effects of E2 on NOS at the mRNA, protein and NO production level. The study of the cellular and molecular effects of E2 on EC function is a vital component to understanding the vasculoprotective effects of ovarian hormones and the future Implications for a therapeutic role of the hormones in cardiovascular disease.
| Blum, Michael; Slade, Martin; Boden, Donna et al. (2004) Examination of gender bias in the evaluation and treatment of angina pectoris by cardiologists. Am J Cardiol 93:765-7 |
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| Caulin-Glaser, T; Farrell, W J; Pfau, S E et al. (1998) Modulation of circulating cellular adhesion molecules in postmenopausal women with coronary artery disease. J Am Coll Cardiol 31:1555-60 |
| Caulin-Glaser, T; Garcia-Cardena, G; Sarrel, P et al. (1997) 17 beta-estradiol regulation of human endothelial cell basal nitric oxide release, independent of cytosolic Ca2+ mobilization. Circ Res 81:885-92 |
