Hormone replacement therapy, smoking &amp; lipoprotein oxidation
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: When women reach menopause, their risk for heart disease increases, in part, because of the aging process and, in part, because their ovaries no longer make estrogen and progesterone. Estrogen is known to reduce cardiovascular risk significantly. Cigarette smoking constitutes a third significant risk factor in postmenopausal women and environmental tobacco smoke (ETS) also contributes to cardiovascular risk in "passive" smokers. Therefore, it appears that the lack of ovarian hormones associated with menopause and exposure to cigarette smoke (passive or active) constitute the two most important risk factors for heart disease in otherwise healthy women. Hormone replacement therapy (HRT), the replacement of estrogen (or estrogen and progesterone) through medication, reduces the risk of heart disease by as much as 50% in postmenopausal women. Yet physicians are hesitant to prescribe HRT for women smokers, due to the historical (albeit rare) occurrence of blood clotting (and the resulting risk of blood vessel occlusion and/or stroke) in women who smoke and take contraceptive pills that contain estrogen. However, the risk of clotting associated with HRT is minimal and increases only slightly in HRT-treated women who smoke. Although the ideal approach to management of heart disease risk in postmenopausal women would include smoking cessation, for those women who chose to continue smoking, or who live in a situation associated with exposure to environmental tobacco smoke, HRT may be an especially important intervention. It is my goal to develop a small animal model for the first rigorous studies of the interactions between environmental tobacco smoke, postmenopausal status and hormone replacement therapy as they relate to heart disease. To this end, I have designed this proposal to accomplish the following specific aims:
 
 
 
 
 
 Aim #1: To test the hypothesis that exposure to environmental tobacco smoke (ETS) will accelerate artery disease in normal mice and to a greater extent, in mice whose ovaries have been removed (postmenopausal mice).
 
 
 
 
 
 Aim #2: To test the hypothesis that estrogen, and estrogen + progesterone, will partially reverse the acceleration in artery plaque formation resulting from removal of the ovaries and from ETS exposure.
 
 
 
 
 
 Aim #3: To test the hypothesis that factors involved in ETS-induced acceleration of artery disease include oxidant stress in addition to increases in cholesterol levels, and that cholesterol levels and oxidant stress are reduced as a result of HRT.
 
 
 
 
 
 The successful completion of these aims will yield valuable information concerning 1) the extent and mechanisms of ETS-mediated acceleration of arterial disease; 2) the additive effects of ETS and postmenopausal status on risk of heart disease; 3) the mechanisms underlying protective effects of estrogens; and 4) the interactions of ETS and hormone replacement therapy.