Establishment of a model for diabetic cardiorenal syndrome in female mRen2.Lewis

描述（由申请人提供）：糖尿病是美国的主要死因之一，也是绝经前和绝经后女性发生心血管（CV）和终末期肾病的公认独立风险因素。与年龄匹配的男性或非糖尿病女性相比，糖尿病女性表现出更高的心血管和肾脏病变患病率。糖尿病患者心肾综合征的最新分类强调心脏和肾脏同时发生损伤和/或功能障碍。重要的是，合并肾和心脏功能不全或衰竭的糖尿病高血压妇女雌激素耗竭显着有助于这些患者的预后不良。缺乏高血压糖尿病女性心肾综合征的体内实验模型限制了我们阐明这种综合征的潜在机制以及开发更有效的治疗方法的能力。本申请旨在在同类mRen2.Lewis大鼠中建立糖尿病心肾综合征的实验模型，该模型反映了雌激素减少的糖尿病高血压女性中心脏和肾脏功能障碍/衰竭的共存。这些研究还将确定新型雌激素受体GPR 30在减缓心肾综合征发展和进展中的作用，这可能揭示减少女性CV疾病的新治疗方法。

DESCRIPTION (provided by applicant): Diabetes is one of the leading causes of death in the United States and a well-recognized independent risk factor for the development of cardiovascular (CV) and end-stage renal disease in premenopausal and postmenopausal women. Diabetic women exhibit a greater prevalence of cardiovascular and renal pathologies as compared to age-matched males or non-diabetic females. The recent classification of cardiorenal syndrome in diabetic patients emphasizes the occurrence of simultaneous injury and/or dysfunction in the heart and kidney. Importantly, the combined renal and cardiac dysfunction or failure in diabetic hypertensive women with estrogen depletion significantly contributes to the poor prognosis for these patients. The absence of an in vivo experimental model of cardiorenal syndrome in hypertensive diabetic females limits our ability to elucidate the underlying mechanisms of this syndrome, as well as the development of more effective therapeutic approaches. This application seeks to establish an experimental model of diabetic cardiorenal syndrome in the congenic mRen2.Lewis rat that reflects the coexistence of cardiac and renal dysfunction/failure in diabetic hypertensive women with reduced estrogen. The studies will also establish the role of the novel estrogen receptor GPR30 to attenuate the development and progression of the cardiorenal syndrome which may reveal new therapeutic approaches to reduce CV disease in women.