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：
8055538
负责人：
BARBARA RANSCHT
金额：
$ 23.88万
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/8055538
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 Inflammatory Knockout Mice Laboratories Lead Ligand Binding Link Mediating Membrane Membrane Glycoproteins Membrane Proteins Metabolic Metabolic Diseases 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）：与肥胖相关的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，与预防与肥胖相关的代谢和心血管功能障碍有关。随着脂肪组织的扩展和低水平的APN降低与冠状动脉疾病，高血压，心脏梗塞和其他心血管功能障碍有关。在心脏肥大和缺血性心脏病的动物模型中，APN的给药可改善病理心肌重塑。虽然APN的有益功能得到很好的描述，但对在心血管系统中启用APN生理功能的膜受体知之甚少。 T-钙粘蛋白是心血管功能中遗传链接分析与遗传链接分析有关的APN结合蛋白，是一种候选细胞表面糖蛋白，可介导APN功能。该R21应用将探索T-钙粘蛋白在心脏病模型中的功能，并将潜在的作用与脂联素的功能联系起来。公共卫生相关性：肥胖症通过改变循环中脂肪细胞分泌的促脂肪细胞和抗炎细胞因子的水平，从而导致代谢和心血管疾病。脂联素是一种脂肪分泌的抗炎细胞因子，在调节代谢和心血管功能方面具有有益的作用。脂联素与心肌细胞和内皮细胞表面相关，以发挥有益的功能。能够使脂联素与细胞表面互动并导致下游信号级联激活的受体保持不足。本应用中提出的研究将探讨T-钙粘蛋白是一种新型的脂联素结合细胞表面糖蛋白，在心脏和脉管系统的功能中。具体而言，提出的实验将测试T-钙粘蛋白是否对于脂联素的心脏保护作用至关重要。这项工作将有助于理解脂联素的心血管保护功能，如果成功 - 构成了探索T-钙粘蛋白 - 磷灰蛋白相互作用的新基础，这是从心血管损伤中恢复的可能药物。