Dorie Schwertz, PhD, BSN, BA, RN, FAAN , FAHA, Funded Projects
Estrogen Effect on Norepinephrine-elicited Hypertrophy in Neonatal Rat Ventricular Myocytes
Funding Source: National Institute of Nursing Research PILOT
Dates: 10/15/05 – 10/15/07
Abstract: The incidence of heart failure (HF) increases with age. The yearly cost of the disease in the USA is estimated to be over 10 billion dollars. The incidence of HF is lower in premenopausal women than age-matched men. However, in the postmenopausal years, the incidence increases and exceeds that of men making it the #1 killer in this vulnerable population. The results of many human and animal studies suggest that estrogen exerts a protective effect against pathological cardiac hypertrophy (CH) and HF. Research suggests that cellular calcium (Ca2 ) overload is central to the development of CH and HF. Virtually all of the key biological signaling molecules involved in development of CH and HF, e.g., norepinephrine (NE), initiate signal transduction via G-protein-coupled (GPC) receptors and elevate intracellular Ca2 . It has been demonstrated chronic NE stimulation acting alone, can produce heart muscle cell hypertrophy and programmed cell death, that transitions into HF. NE binds to 4 GPC adrenergic receptors (ARs - a1A-AR, a1B-AR, 1-AR, and 2-AR) and each of these receptors differentially modulate (increase or decrease) intracellular Ca2 . The long-term goal of our research is to elucidate underlying physiological mechanisms that contribute to the cardioprotective effects of estrogen. In this study, we will use a cultured neonatal rat ventricular myocyte (NRVM) model to begin to examine the overall hypothesis that estrogen-elicited alteration in the expression of ARs mediates protection against CH and HF. Aims include: 1) to begin to determine the effect of estrogen on AR expression, 2) to validate a model of NE-induced heart muscle cell hypertrophy in NRVMs, and 3) to demonstrate an estrogen-elicited reduction of the NE-induced hypertrophic response in NRVMs. Pilot data derived from the study will position us to apply for RO1 funding to address the question; whether estrogen-mediated alterations in AR expression are correlated with a reduction in NE-induced hypertrophy, programmed cell death (a marker of HF) and are responsible, at least in part, for estrogen-elicited cardioprotection.