ABSTRACT
Prior to menopause women have a lower incidence and severity of coronary artery disease compared to men of the same age (Barrett-Conner and Bush, 1991). After menopause this difference diminishes unless estrogen replacement therapy is initiated (Eaker et al., 1993; Stampfer and Colditz, 1991). Such observations suggest that estrogen provides protection against the development of cardiovascular disease [for reviews see, (Wenger, 1990; Barrett-Conner and Bush, 1991; Eaker et al., 1993; Stampfer and Colditz, 1991; Riedel et al., 1993)]. Estrogenic regulation of multiple components of the vessel wall has been proposed as a major mechanism to account for the “cardioprotective” effects of estrogen. Indeed, both the vascular endothelium (Kim-Schulze et al., 1996; Venkov et al., 1996) and smooth muscle (Horwitz and Horwitz, 1982; Orimo et al., 1993; Karas et al., 1994; Harder and Coulson, 1979; McGill and Sheridan, 1981; Losordo et al., 1994; Kaplan et al., 1992) express functional estrogen receptors which have the potential to regulate over 30 genes associated with the development of cardiovascular disease (Mendelsohn and Karas, 1994). The vascular endothelium acts as a dynamic regulatory interface between the blood and media and therefore represents a target through which estrogen might regulate vascular remodeling. Exactly how estrogen interacts with the vascular endothelium is unclear, but attention to date has focused on estrogenic regulation of those endothelium-derived relaxing factors which are generally believed to be salutary in nature such as nitric oxide and prostacyclin. Alternatively, estrogen may regulate endothelium-derived contractile factors, a number of which are mitogenic and/or thrombogenic
* Corresponding author, Tel.: 0015072842290, Fax: 0015072845075, E-mail: miller.virginia@mayo.edu.
