Opioidergic System in Development of Heart Failure

心力衰竭发展中的阿片系统

基本信息

批准号：
7313931
负责人：
JOEL J SCHULTZ
金额：
$ 24.86万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7313931
关键词：
Abscess Acceleration Acute Adult Affect Agonist Animal Organ Attenuated Biochemical Biological Biological Markers Cardiac Cardiomyopathies Cardiovascular Diseases Cardiovascular system Caring Catheterization Cell Proliferation Regulation Cellulitis Chronic Clinical Condition Data Deterioration Development Early treatment Echocardiography Etiology Exposure to Failure Functional disorder Goals Growth Hamsters Heart Heart Diseases Heart Hypertrophy Heart failure Human Hypertension Hypertrophic Cardiomyopathy Infection Infective endocarditis Left Ligands Liver diseases Lung Medical Methods Modeling Modification Molecular Molecular Biology Morphine Myocardial Opiate Addiction Opiates Opioid Opioid Peptide Opioid Receptor Pathogenesis Pathology Patients Pattern Peptides Personal Satisfaction Pharmaceutical Preparations Pharmacology Phenotype Physiological Physiology Plasma Play Pneumonia Predisposition Prevention Principal Investigator Public Health Rate Receptor Activation Recovery Relaxation Research Role Staging Study Section System Systolic Pressure Techniques Testing United States Veins Ventricular Work base endogenous opioids heart function improved insight interdisciplinary approach normotensive novel novel diagnostics opioid abuse programs receptor receptor expression receptor function response

项目摘要

DESCRIPTION (provided by applicant): The overall objective of this proposal is to investigate whether the alterations in the opioidergic system modulate the development and progression of heart failure. Although infective endocarditis is well- documented to occur and its clinical features well described in opiate addicts, few studies have focused on the acute or chronic effects of opiates on heart diseases other than infective endocarditis. Likewise, the role of the opioidergic system in the deterioration of heart function remains entirely speculative. A broad multidisciplinary approach will be established that combines diverse techniques (integrative physiology, molecular biology, and pharmacology) and will integrate basic information at the cellular level with information at the whole organ/animal level. To ascertain the involvement of the opioidergic system in the progression of heart failure, we will assess mu-, delta-, and kappa-opioid receptor expression and functionality as well as alterations in endogenous opioid peptide precursors and their peptide products at various stages in the progression of heart failure via molecular and pharmacological methods. Furthermore, the cardiac effects (i.e, remodeling and function) during chronic opiate/opioid administration or opioid receptor antagonism will be evaluated by echocardiography and left ventricular catheterizations along with histological and morphological techniques. A unique hamster strain which is predisposed to hypertrophic cardiomyopathy and heart failure will be used to test the involvement of the opioidergic system in the development and progression to heart failure and how each opioid receptor type modulates the progression to heart failure following chronic opiate/opioid abuse. Results of this proposal will provide novel insights into the relationship between heart failure and the opioidergic system, as modulated by chronic opiate/opioid use. Opiate addiction and cardiovascular disease are prevalent as well as costly public health issues in the United States. Understanding the molecular and cellular basis of the opioidergic system in heart failure is a necessary step towards elucidating its role in cardiovascular disease. These findings may prove to be useful in identifying novel diagnostic or biomarkers for a predisposition to or early stages of heart failure, thus allowing earlier treatment and prevention in susceptible patients. Also, these findings may result in reassessment of medical care and treatment in patients exposed to chronic opiate/opioid administration.

描述（由申请人提供）：该提案的总体目标是研究阿片类药物系统的改变是否调节心力衰竭的发生和进展。尽管阿片类药物成瘾者感染性心内膜炎的发生及其临床特征已有充分记录，但很少有研究关注阿片类药物对感染性心内膜炎以外的心脏病的急性或慢性影响。同样，阿片类药物系统在心脏功能恶化中的作用仍然完全是推测性的。将建立广泛的多学科方法，结合不同的技术（综合生理学、分子生物学和药理学），并将细胞水平的基本信息与整个器官/动物水平的信息整合起来。为了确定阿片能系统在心力衰竭进展中的参与，我们将评估 mu-、delta-和 kappa-阿片受体的表达和功能，以及内源性阿片肽前体及其肽产物在心力衰竭各个阶段的变化。通过分子和药理学方法治疗心力衰竭的进展。此外，将通过超声心动图和左心室导管插入术以及组织学和形态学技术来评估长期阿片/阿片类药物给药或阿片类药物受体拮抗作用期间的心脏效应（即重塑和功能）。一种易患肥厚性心肌病和心力衰竭的独特仓鼠品系将用于测试阿片能系统在心力衰竭发生和进展中的参与情况，以及每种阿片受体类型如何调节慢性阿片/阿片类药物滥用后心力衰竭的进展。该提案的结果将为心力衰竭与阿片系统之间的关系提供新的见解，该系统受长期阿片/阿片类药物使用的调节。在美国，阿片成瘾和心血管疾病以及代价高昂的公共卫生问题都很普遍。了解心力衰竭中阿片能系统的分子和细胞基础是阐明其在心血管疾病中的作用的必要步骤。这些发现可能有助于确定心力衰竭易感性或早期阶段的新诊断或生物标志物，从而可以对易感患者进行早期治疗和预防。此外，这些发现可能会导致对长期使用阿片/阿片类药物的患者的医疗护理和治疗进行重新评估。