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：
8227676
负责人：
MARK C CHAPPELL
金额：
$ 22.2万
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 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8227676
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. PUBLIC HEALTH RELEVANCE: Cardiovascular disease (CVD) is leading cause of death for women in the US and the identification of the cardiorenal syndrome (the interrelationship between cardiac and renal dysfunction) may have important implications regarding the early diagnosis and treatment of CVD in women, particularly with diabetes as an additional complicating factor. The proposed project addresses a critical issue in the cardiorenal syndrome through the development of a robust experimental model in the diabetic hypertensive mRen2.Lewis strain and assessment of the novel estrogen receptor GPR30.

描述（申请人提供）：糖尿病是美国的主要死亡原因之一，也是良好认可的独立危险因素，用于发展心血管（CV）和绝经后妇女的终末期肾脏疾病。与年龄匹配的雄性或非糖尿病女性相比，糖尿病妇女的心血管和肾脏病变患病率更高。糖尿病患者最近对心脏综合征的分类强调了心脏和肾脏同时受伤和/或功能障碍的发生。重要的是，雌激素消耗的糖尿病性高血压妇女的肾功能障碍和心脏功能障碍或失败显着导致这些患者的预后不良。高血压糖尿病女性中心脏综合征的体内实验模型的缺乏限制了我们阐明该综合征的基本机制的能力，以及开发更有效的治疗方法。该应用旨在在先天性Mren2.Lewis大鼠中建立一个糖尿病心脏综合征的实验模型，该模型反映了心脏和肾功能障碍/失败的糖尿病性高血压女性的共存，雌激素降低。这些研究还将确定新型雌激素受体GPR30在减轻心脏综合征的发育和进展方面的作用，这可能揭示了减少女性CV疾病的新治疗方法。公共卫生相关性：心血管疾病（CVD）是美国女性的主要死亡原因，并且鉴定心脏综合征（心脏和肾功能障碍之间的相互关系）可能对女性的早期诊断和治疗女性具有重要意义，尤其是在糖尿病中，糖尿病是其他并发因子。提出的项目通过在糖尿病性高血压MREN2.LEWIS菌株中开发出强大的实验模型和新型雌激素受体GPR30的评估来解决心脏综合征中的关键问题。