Substantial evidence exists regarding the favorable influence of estrogen on cardiovascular outcomes in women. These favorable effects extended beyond those explained by estrogen effects on lipid profile and other recognized risk factors. Accumulating evidence strongly supports that these favorable outcomes are in part due to direct effects of estrogen on estrogen receptors expressed in cardiovascular tissues, including both the vasculature and myocardium. Attenuating the untoward effects o current hormone replacement strategies on non-cardiovascular tissues such as uterus and breast by development of tissue selective estrogen modulators (SERMS) will likely provide novel strategies for the treatment of bone, neurologic and cadiovascular diseases. Raloxifene, the first SERM approved, was relased recently for prevention of osteoporosis, but data, including new data presented in the SCOR (Project 3) support the hypothesis that raloxifene also directly activates the estrogen receptors now known to be expressed in the cardiovascular system. This project will examine the effects of raloxifene on parameters of cardiovascular structure and function in a population of post-menopausal women who have had a myocardial infarction (MI). We will test the hypothesis that raloxifene directly and favorably influences cardiovascular function following MI, in four specific aims.
The Specific Aims are to examine indices of: 1. Left ventricular remodeling; 2. Endothelial function; 3. Autonomic tone and neurohormonal activation; 4. Vulnerability to ventricular arrhythmias. This study directly and prospectively tests the overall SCR hypothesis in a human population and will further our understanding of the underlying mechanisms by which estrogen receptor modulation may diminish the burden of cardiovascular diseases and their sequelae in women. Moreover, this study initiates and area of clinical investigation with potential implications for the therapy of ischemic cardiovascular diseases in both women and men.
|Nowak, Kristen L; You, Zhiying; Gitomer, Berenice et al. (2018) Overweight and Obesity Are Predictors of Progression in Early Autosomal Dominant Polycystic Kidney Disease. J Am Soc Nephrol 29:571-578|
|Lamon-Fava, Stefania; Diffenderfer, Margaret R; Barrett, P Hugh R et al. (2018) Differential Effects of Estrogen and Progestin on Apolipoprotein B100 and B48 Kinetics in Postmenopausal Women. Lipids 53:167-175|
|Askie, Lisa M; Darlow, Brian A; Finer, Neil et al. (2018) Association Between Oxygen Saturation Targeting and Death or Disability in Extremely Preterm Infants in the Neonatal Oxygenation Prospective Meta-analysis Collaboration. JAMA 319:2190-2201|
|Dad, Taimur; Abebe, Kaleab Z; Bae, K Ty et al. (2018) Longitudinal Assessment of Left Ventricular Mass in Autosomal Dominant Polycystic Kidney Disease. Kidney Int Rep 3:619-624|
|Brosnahan, Godela M; Abebe, Kaleab Z; Rahbari-Oskoui, Frederic F et al. (2017) Effect of Statin Therapy on the Progression of Autosomal Dominant Polycystic Kidney Disease. A Secondary Analysis of the HALT PKD Trials. Curr Hypertens Rev 13:109-120|
|Di Fiore, Juliann M; Martin, Richard J; Li, Hong et al. (2017) Patterns of Oxygenation, Mortality, and Growth Status in the Surfactant Positive Pressure and Oxygen Trial Cohort. J Pediatr 186:49-56.e1|
|Scherzer, Rebecca; Heymsfield, Steven B; Rimland, David et al. (2017) Association of serum albumin and aspartate transaminase with 5-year all-cause mortality in HIV/hepatitis C virus coinfection and HIV monoinfection. AIDS 31:71-79|
|Torres, Vicente E; Abebe, Kaleab Z; Schrier, Robert W et al. (2017) Dietary salt restriction is beneficial to the management of autosomal dominant polycystic kidney disease. Kidney Int 91:493-500|
|Younge, Noelle; Goldstein, Ricki F; Bann, Carla M et al. (2017) Survival and Neurodevelopmental Outcomes among Periviable Infants. N Engl J Med 376:617-628|
|Irazabal, María V; Abebe, Kaleab Z; Bae, Kyongtae Ty et al. (2017) Prognostic enrichment design in clinical trials for autosomal dominant polycystic kidney disease: the HALT-PKD clinical trial. Nephrol Dial Transplant 32:1857-1865|
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