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Role of T-Cadherin in Adiponection-mediated cardiovascular functions

T-钙粘蛋白在脂肪连接介导的心血管功能中的作用

基本信息

批准号：
7877109
负责人：
BARBARA RANSCHT
金额：
$ 28.65万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-02 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7877109
关键词：
Address Adipocytes Adipose tissue Age Animal Model Anti-Inflammatory Agents Anti-inflammatory Binding Binding Proteins Binding Sites Biochemical Biology Blood Circulation Cadherins Cardiac Cardiac Myocytes Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cell surface Cells Coronary Arteriosclerosis Defect Docking Drug Delivery Systems Endothelial Cells Epidemiologic Studies Fatty acid glycerol esters Functional disorder Genes Grant H-Cadherin Heart Heart Diseases Heart Hypertrophy Human Hypertension Knockout Mice Laboratories Lead Ligand Binding Link Mediating Membrane Membrane Glycoproteins Membrane Proteins Metabolic Metabolic syndrome Modeling Molecular Mus Mutant Strains Mice Mutation Myocardial Infarction Myocardial Ischemia Obesity Physiological Recovery Research Risk Factors Role Serum Signal Pathway Signal Transduction Suggestion Testing Tissues Vascular remodeling Ventricular Remodeling Wild Type Mouse Work adiponectin base cardiovascular injury constriction cytokine genetic linkage genetic linkage analysis heart function improved in vivo mouse model mutant novel public health relevance receptor research study response

项目摘要

DESCRIPTION (provided by applicant): Obesity-related metabolic syndrome is major risk factor for cardiovascular diseases. Adiponectin (APN), a circulating fat-secreted cytokine, is implicated in protecting against obesity-related metabolic and cardiovascular dysfunctions. Levels of APN decrease with the expansion of adipose tissue and low levels are associated with coronary artery disease, hypertension, heart infarct and other cardiovascular dysfunctions. In animal models of cardiac hypertrophy and ischemic heart disease, administration of APN improves pathological myocardial remodeling. While the beneficial functions of APN are well described, little is known about membrane receptors that enable APN's physiological functions in the cardiovascular system. T-cadherin, an APN binding protein implicated by genetic linkage analysis in cardiovascular functions, is a candidate cell surface glycoprotein to mediate APN functions. This R21 application will explore the functions of T-cadherin in a mouse model of heart disease and relate a potential role to the functions of adiponectin. PUBLIC HEALTH RELEVANCE: Obesity contributes to metabolic and cardiovascular disorders by altering the levels of adipocyte-secreted pro- and anti-inflammatory cytokines in the circulation. Adiponectin is a fat-secreted anti-inflammatory cytokine with beneficial actions in regulating metabolic and cardiovascular functions. Adiponectin associates with cardiomyocyte and endothelial cell surfaces to exert beneficial functions. The receptors that enable the engagement of adiponectin with cell surfaces and lead to activation of downstream signaling cascades remain poorly understood. Research proposed in this application will explore the contributions of T- cadherin, a novel adiponectin-binding cell surface glycoprotein, in functions of the heart and vasculature. Specifically, the proposed experiments will test if T-cadherin is essential for the cardioprotective actions of adiponectin. This work will contribute to understanding adiponectin's cardiovascular-protective functions and - if successful - form a new basis for exploring the T-cadherin-adiponectin interaction as a possible drug target for recovery from cardiovascular injury.

描述（由申请人提供）：肥胖相关代谢综合征是心血管疾病的主要危险因素。脂联素（APN）是一种循环脂肪分泌的细胞因子，与预防肥胖相关的代谢和心血管功能障碍有关。APN水平随着脂肪组织的扩张而降低，低水平与冠状动脉疾病、高血压、心脏梗死和其他心血管功能障碍有关。在心肌肥厚和缺血性心脏病动物模型中，APN可改善病理性心肌重构。虽然APN的有益功能已被很好地描述，但对使APN在心血管系统中发挥生理功能的膜受体知之甚少。t -钙粘蛋白（T-cadherin）是一种介导APN功能的候选细胞表面糖蛋白，与心血管功能的遗传连锁分析有关。这个R21应用程序将探索t -钙粘蛋白在心脏病小鼠模型中的功能，并将其与脂联素的功能联系起来。