Endocrine Abstracts

In the 1990s, we learned that the same estrogen receptors that mediate hormonal effects in reproductive tissues also function in the heart and blood vessels, where they are required for normal cardiovascular physiology and for estrogen-mediated protection against vascular injury and atherosclerosis. Great progress has been made in the past decade in understanding the importance of ERα and ERβ in cardiovascular physiology and disease. In this presentation, data regarding the specific role of ERs in cardiovascular physiology and pathophysiology will be reviewed and biological explanations for the WHI-generated controversy and confusion regarding hormone replacement therapy (HRT) will be highlighted. Newer clinical evidence that more firmly supports the beneficial cardiovascular effects of HRT for menopausal women also will be reviewed and explained in the context of basic science and animal studies from the past 15 years that clearly support a central protective role for estrogen and ERs in cardiovascular disease. Molecular and cellular explanations for the controversy that arose from the Women’s Health Initiative (WHI) trials of the cardiovascular effects of HRT on CVD will be discussed and differences in the underlying vascular biology that exists between younger and older menopausal women that support the importance of timing of HRT initiation will be reviewed. Several newer concepts in sex steroid hormone receptor action that have important implications for cardiovascular physiology and disease also will be discussed. These include the role of receptor co-regulatory proteins in cardiovascular cell biology, rapid (‘non-genomic’) activation of vascular endothelial cells by estrogen and ERs, ligand-independent ER activation in vascular cells, gender differences in regulation of metabolic pathways important to cardiovascular diseases by other NHR, and genetic ER variants associated with altered cardiovascular risk in both sexes. The ways in which these newer pathways can add substantial combinatorial complexity to the physiological effects of estrogen in target cardiovascular tissues will be discussed.