Vascular Remodeling is a Crucial Factor in the Progression of Hypertrophic Cardiomyopathy

血管重塑是肥厚型心肌病进展的关键因素

基本信息

批准号：
10396644
负责人：
Richard Marszalek
金额：
$ 4.96万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10396644
关键词：
Acoustics Acute Adolescent Affect Age Agonist Area Arteries Automobile Driving Biochemical Blood Blood Vessels Blood flow Cardiac Cardiac Myocytes Cardiovascular Diseases Cells Characteristics Clinical Clinical Research Complement Contrast Media Coronary Coronary artery Data Dependence Detection Diastole Disease Disease Progression Dyes Echocardiography Elements Endothelial Cells Endothelium Fibrosis Flow Cytometry Functional disorder Generations Genetic Diseases Growth Heart Histologic Histology Human Hydrogen Peroxide Hypertrophic Cardiomyopathy Hypertrophy Immunohistochemistry Impairment Investigation Ischemia Link Measures Mechanics Mediating Mediator of activation protein Microvascular Dysfunction Modeling Modification Molecular Morphology Muscle Cells Mutation Myocardial Myocardial dysfunction Myocardial tissue Myocardium Nitric Oxide Pathologic Pathway interactions Patients Perfusion Physiological Play Process Proteins Reactive Oxygen Species Regulation Relaxation Research Role Signal Transduction Specificity Specimen Stress Techniques Testing Therapeutic Tissues Vascular Diseases Vascular remodeling Vasodilator Agents Ventricular Ventricular Remodeling Western Blotting analog arteriole blood perfusion cell type cytokine drug development effective therapy endothelial dysfunction experimental study heart function hypoperfusion multiple sclerosis treatment novel novel marker novel therapeutic intervention postnatal postnatal development pre-clinical preservation prevent programs response sphingosine 1-phosphate stressor

项目摘要

Abstract: Our investigations into the early irreversible progression in hypertrophic cardiomyopathy and the lack of effective treatments has led us to concentrate on the coronary microvasculature. Clinical studies have been characterizing the deleterious vascular alterations occurring in the disorder, but further investigations into the underlying mechanisms behind this relationship have been minimal. The experiments proposed within the proposal will begin to answer the role perfusion and vascular dysfunction play in the progression of hypertrophic cardiomyopathy. Given the mechanical and energetic deficiencies in the disorder, it is likely that they impede physiological coronary flow that drives remodeling of vessels. These relationships and influencing factors will be looked more closely into. The endothelial dysfunction within the myocardium is expected to have a substitution of the primary vasodilator nitric oxide to ROS signaling as is stereotypical of vascular dysfunction. We will therefore make efforts to understand this switch between vasoactive molecules and its impact on coronary alterations. We will lastly attempt to modify the endothelial function in hypertrophic cardiomyopathy with an sphingosine-1-phosphate analog, FTY720, to prevent the irreversible progression established early on.

抽象的：我们对肥厚性心肌病的早期不可逆进展的调查以及缺乏有效的治疗使我们专注于冠状动脉微举行。临床研究一直在表征该疾病中发生的有害血管改变，但进一步研究了基础这种关系背后的机制很少。提案中提出的实验将开始回答肥厚型进展中灌注和血管功能障碍的作用心肌病。鉴于该疾病的机械和能量缺陷，它们可能会阻碍驱动血管重塑的生理冠状动脉流。这些关系和影响因素将是更仔细地研究。心肌内的内皮功能障碍有望取代刻板印象的血管舒张剂一氧化氧化氧化氧化氧化氧化物的刻板印象是血管功能障碍。我们将因此，努力了解血管活性分子之间的这种转变及其对冠状动脉的影响改变。最后，我们将尝试修改肥厚性心肌病中的内皮功能鞘氨醇1-磷酸类似物FTY720，以防止早期建立的不可逆进展。