Biochemical Markers of Progressive Heart Disease

进行性心脏病的生化标志物

基本信息

批准号：
8247680
负责人：
Peter N. Buttrick
金额：
$ 19.13万
依托单位：
UNIVERSITY OF COLORADO DENVER
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：
2011-04-01 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8247680
关键词：
Adrenergic beta-Antagonists Affect American Animal Model Antibodies Biochemical Biochemical Markers Biopsy Calcium Cardiac Cause of Death Clinical Complex Contractile Proteins Defect Depressed mood Development Diagnostic Disease Elements Functional disorder Generations Genetic Transcription Goals Grant Heart Heart Diseases Heart Transplantation Heart failure Human Implantable Defibrillators In Situ Individual Laboratories Lead Link Microfilaments Muscle Muscle Cells Myocardium Nature Pathologic Patients Pattern Performance Phosphoproteins Phosphorylation Post-Translational Protein Processing Preparation Process Property Protein Microchips Proteins Relaxation Research Personnel Role Series Severities Signal Pathway Signal Transduction Pathway Site Societies Staging Stress Time Tissue Sample Tissues Translations Troponin I Troponin T Work base design disability human subject myosin-binding protein C novel protein profiling public health relevance reconstitution response tool

项目摘要

DESCRIPTION (provided by applicant): The adaptational response of the heart to a pathologic stress is a complex process that reflects the nature, severity and duration of the insult. Many of these cellular changes have a negligible impact on the integrated performance of the heart however some have been shown to be critically important in moderating force generation and relaxation, properties that define integrated cardiac performance. In this proposal we propose to develop a unique diagnostic tool, a phosphoprotein antibody chip that can be used to define potentially tractable alterations in the maladaptive heart that might be amenable to targeted therapy. Two complementary approaches will be imbedded in this chip, the first is the inclusion of existing antibody probes that target signaling pathways known to be altered in maladaptive heart disease and the second will be the development and inclusion of a series of novel phosphoantibodies directed against specific sarcomeric protein sites that have been shown to have functional significance in reconstituted myofibrillar preparations. Finally we will validate this diagnostic tool using tissue from well characterized animal models as well as from humans with clinical heart failure. PUBLIC HEALTH RELEVANCE: Heart failure is a leading cause of death and disability in Western society, affecting more than 5 million Americans. The disease affects many aspects of the heart but one fundamental defect resides at the level of the contractile elements within the muscle. Changes in myofilament protein status underlie functional changes in the heart. The goal of this proposal is to design a diagnostic tool (a protein antibody chip) that will allow an assessment of disease status based on the myofilament protein profile. Furthermore, this tool may also be used to identify potentially tractable features of the muscle that lead to novel therapies.

描述（由申请人提供）：心脏对病理压力的适应性反应是一个复杂的过程，反映了侮辱的性质，严重性和持续时间。这些细胞变化中的许多变化对心脏的综合性能具有可忽略的影响，但是一些细胞变化在调节力的产生和放松方面至关重要，这些特性定义了综合的心脏表现。在此提案中，我们建议开发一种独特的诊断工具，一种磷蛋白抗体芯片，可用于定义可能适合靶向治疗的不良适应性心脏的潜在疗法改变。 Two complementary approaches will be imbedded in this chip, the first is the inclusion of existing antibody probes that target signaling pathways known to be altered in maladaptive heart disease and the second will be the development and inclusion of a series of novel phosphoantibodies directed against specific sarcomeric protein sites that have been shown to have functional significance in reconstituted myofibrillar preparations.最后，我们将使用来自特征性动物模型的组织以及具有临床心力衰竭的人类的组织来验证这种诊断工具。公共卫生相关性：心力衰竭是西方社会死亡和残疾的主要原因，影响了超过500万美国人。该疾病会影响心脏的许多方面，但是一个基本缺陷属于肌肉内收缩元素的水平。心脏功能变化是肌丝蛋白状态的变化。该建议的目的是设计一种诊断工具（一种蛋白质抗体芯片），该工具将允许根据肌丝蛋白概况评估疾病状态。此外，该工具也可用于识别导致新疗法的肌肉的潜在疗程特征。