Project: Research project

Project Details


Estrogens may provide a "protective action" against cardiovascular
disease for premenopausal women. Additionally, the outcome for
postmenopausal women following interventional coronary artery procedures
is worse than the outcome for men. The reasons for this are unclear.
The unifying hypothesis of this proposal is that sex hormonal status
affects expression of hormone receptors (estrogen, progesterone and
androgen) which in turn regulates structural and functional
characteristics of coronary arteries. The experiments of this proposal
represent a collaboration among established investigators in the areas
of endocrine, endothelia and muscle physiology. Receptor binding assays
will be used to quantify the number of affinity of receptors for
estrogen, progesterone and androgen in coronary arteries of sexually
mature male, female and ovariectomized female pigs (Specific Aim 1).
Structural characteristics of the arterial wall will be studied using
molecular techniques to characterize matrix proteins in the arterial wall
and their regulation by sex hormones. These proteins dictate the
viscoelastic properties of the arterial wall which will be defined in
isolated strips of coronary arterial smooth muscle (Specific Aim 2). The
effects of sex hormonal status on the functional characteristics of the
arteries will be evaluated using a combination of molecular, cell culture
and isolated tissue techniques. These functional characteristics include
the relationship of sex hormones and expression of hormone receptors on
cell proliferation, the production of endothelium-derived nitric oxide
and endothelins, the number and affinity of endothelin-receptors on the
smooth muscle, and the effects of sex steroids on sensitivity (Specific
Aim 3). All results will be assessed relative to the hormonal status of
the animal as defined by circulating sex steroid hormones and the number
of estrogen receptors. Results form these studies will provide new
information about the regulation of sex steroid receptors and how they
may affect the structure and function of coronary arteries. By
understanding these basic regulatory mechanisms, potentially selective
therapies can be developed for prevention and treatment of coronary
artery disease in humans.
Effective start/end date12/1/936/30/04


  • Medicine(all)