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Cardiovascular Peptides and Myocardial Infarction

心血管肽与心肌梗塞

基本信息

批准号：
7269302
负责人：
John C Burnett
金额：
$ 49.17万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7269302
关键词：
Acute myocardial infarction Adrenergic Agents Aldosterone Animals Anterior Apoptotic Area Arts Atrial Natriuretic Factor Biological Biological Markers Biology Blood Vessels Blood capillaries Cardiac Cardiac Myocytes Cardiovascular system Cell Survival Cells Collagen Complication Coronary Coronary Arteriosclerosis Development Dilatation - action Disruption Excretory function Fibroblasts Fibrosis Functional disorder Genes Genetic Polymorphism Goals Heart Heart Injuries Heart failure Hormones Hour Human Hypertension Impairment Intravenous Kidney Laboratory Research Lead Magnetic Resonance Imaging Mediating Methodology Modeling Molecular Mus Mutation Myocardial Myocardial Infarction Myocardium Natriuresis Natriuretic Peptides Natural regeneration Nuclear Outcome Oxygen Consumption Pathological Dilatation Peptides Phase Phenotype Phosphotransferases Physiological Plasma Prevention Property Proteins Renal function Renin-Angiotensin-Aldosterone System Reporting Research Research Personnel Risk Sodium Structure System Therapeutic Therapeutic Agents Thinking Time Translational Research Vasodilation Vasodilation disorder Ventricular Ventricular Dysfunction Ventricular Remodeling Wild Type Mouse ZYX gene adrenergic base capillary cardiogenesis clinically relevant day density human study innovation mortality mouse model novel prevent programs promoter repaired response success

项目摘要

DESCRIPTION (provided by applicant): Our objective is to establish that the cardiac peptide BNP is a novel and efficacious therapy for human acute myocardial infarction (AMI) to preserve myocardial structure and function. This highly translational research takes advantage of the cardioprotective and renal enhancing properties of this small and endogenous peptide in protecting the heart from injury and promoting cardiac repair. Our broad unifying hypothesis is that the endogenous natriuretic peptide (NP) system mediates cardiorenal protection and that therapeutic enhancement in experimental and human AMI with exogenous BNP will preserve myocardial structure and function while maintaining renal function. This strategy is based on the biology of BNP that enhances renal function, mediates coronary vasodilatation, reduces myocardial oxygen consumption, suppresses aldosterone release, retards adrenergic activation, induces vascular regeneration, inhibits cardiac fibroblast collagen synthesis and has anti-apoptotic properties. First, we will utilize a murine model of partial proANP gene disruption (Nppa+/-) that has clinical relevance to the recently reported human polymorphism (C664G) that is reported to be characterized by a distruption of the ANP promoter with reduced circulating ANP and risk for ventricular remodeling in human hypertension. This novel genetically altered model has normal cardiac phenotype but demonstrates an exaggerated ventricular hypertrophic and fibrotic response to AMI. In this model with AMI and in wild type (WT) mice we seek to establish cardiorenal protection with 5 days of BNP based therapy. Second, we will extend our research to human AMI investigating the cardiorenal protective properties of 72 hours of BNP therapy initiated at the time of revascularization compared to conventional therapy to preserve myocardial and renal function. Our Specific Aims are as follows: Aim 1: To characterize myocardial structure and function, humoral function and renal function in WT and Nppa+/- mice after AMI; Aim 2: To characterize myocardial structure and function, humoral function and renal function in WT and Nppa+/- mice after AMI in the presence of BNP therapy; and Aim 3: To characterize myocardial structure and function, humoral function and renal function in human AMI in the presence and absence of BNP therapy. For the public, this research may enhance long-term survival after a heart attack. The use of a hormone made in the heart and given at the time of heart attack may help the heart protect and repair itself.