Several studies have identified that women have a survival advantage from symptomatic heart failure. In the FIRST study, the investigators observed this gender difference exclusively among patients with an idiopathic cardiomyopathy. One potential explanation for this observation may be sex-related differences in the remodeling process. I have recently demonstrated that sex-based differences in LV remodeling exist exclusively among patients with an ischemic cardiomyopathy awaiting transplant but not among patients with an end-stage idiopathic cardiomyopathy. Utilizing the minority supplemental grant program to receive initial training in basic science research, I focused my research efforts in understanding sex-based differences in the pathophysiology of heart failure. My immediate career goals are to expand my initial research efforts in this area and further define gender-specific differences in contractile reserve with estrogen deficiency and after myocardial infarction. My long term career goal is to successfully function as an independent research investigator in the area of menopause and cardiovascular disease. My career development plan involves expanding my technical skills in cardiac mechanics and advancing my scientific expertise in the area of women's health. This application involves estrogen's modulation of AT1 receptor expression and local myocardial growth factors, such as; angiotensin II, and the resulting changes in cellular and organ hypertrophy after infarction. This study will test the hypothesis that estrogen deficiency leads to enhanced AT1 receptor expression and an enhanced contractile reserve. A final hypothesis is that estrogen-induced differences in activation of the renin-angiotensin system influence remodeling of the left ventricle and the progression toward decompensated heart failure.
The Specific Aims are to: 1) Determine the effects of estrogen withdrawal (in rats) on cardiac structural remodeling in normal females (compared to hormonally intact males). 2) Determine the effects of estrogen withdrawal on cardiac structural remodeling after infarction using myocyte morphometric analysis. 3) Determine if estrogen status affects the contractile reserve in normal myocardium and after myocardial infarction in females, in comparison to hormonally intact males.
| Rosano, Jenna M; Cheheltani, Rabee; Wang, Bin et al. (2012) Targeted Delivery of VEGF after a Myocardial Infarction Reduces Collagen Deposition and Improves Cardiac Function. Cardiovasc Eng Technol 3:237-247 |
| Gleeson, Deborah; Crabbe, Deborah L (2009) Emerging concepts in cardiovascular disease risk assessment: where do women fit in? J Am Acad Nurse Pract 21:480-7 |
