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

雌性mRen2.Lewis糖尿病心肾综合征模型的建立

基本信息

批准号：
8388799
负责人：
MARK C CHAPPELL
金额：
$ 17.61万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-12-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8388799
关键词：
Address Affinity Age Agonist Angiotensinogen Angiotensins Anti-Inflammatory Agents Anti-inflammatory Attenuated Biochemical Blood Pressure Blood Vessels Cardiac Cardiovascular Diseases Cardiovascular system Cause of Death Cell membrane Characteristics Chronic Cicatrix Classification Combined Modality Therapy Complex Data Development Diabetes Mellitus Diet Early Diagnosis Early treatment End stage renal failure Estrogen Receptors Estrogens Exhibits Experimental Models Failure Female Fibrosis Functional disorder Funding G-Protein-Coupled Receptors Goals Heart Hypertension Incidence Inflammatory Injury Kidney Kidney Diseases Microalbuminuria Modeling Ovarian Pathology Patients Peptidyl-Dipeptidase A Pilot Projects Postmenopause Premenopause Prevalence Protein Precursors Rattus Regulation Renin-Angiotensin System Risk Factors Role Sodium Chloride Syndrome Therapeutic United States Vasoconstrictor Agents Woman arm cardiovascular risk factor congenic diabetic diabetic patient hemodynamics improved in vivo indexing male non-diabetic novel novel therapeutic intervention outcome forecast premature pressure receptor receptor expression urinary

项目摘要

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.

描述(申请人提供)：糖尿病是美国的主要死亡原因之一，也是绝经前和绝经后妇女患心血管疾病(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。最近对糖尿病患者心肾综合征的分类强调心脏和/或肾脏同时发生损伤和/或功能障碍。重要的是，合并雌激素缺乏的糖尿病高血压患者合并心脏和肾功能障碍或衰竭是导致这些患者预后不良的重要原因。高血压糖尿病女性缺乏心肾综合征的体内实验模型，限制了我们阐明该综合征的潜在机制以及开发更有效的治疗方法的能力。本申请旨在建立同源基因mRen2.Lewis大鼠糖尿病心肾综合征的实验模型，反映雌激素水平降低的糖尿病高血压女性心脏和肾功能障碍/衰竭的共存。这些研究还将确定新型雌激素受体GPR30在减缓心肾综合征的发展和进展中的作用，这可能会揭示减少女性心血管疾病的新的治疗方法。