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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：我们对肥厚型心肌病早期不可逆进展的研究以及缺乏有效的治疗方法治疗使我们专注于冠状动脉微血管。临床研究已表征该疾病中发生的有害血管改变，但需要进一步研究潜在的原因这种关系背后的机制微乎其微。提案中提出的实验将开始回答灌注和血管功能障碍在肥厚进展中的作用心肌病。考虑到这种疾病的机械和能量缺陷，它们很可能会阻碍驱动血管重塑的生理性冠状动脉血流。这些关系和影响因素将更仔细地观察。心肌内的内皮功能障碍有望替代主要血管扩张剂一氧化氮与 ROS 信号传导的关系，这是血管功能障碍的典型表现。我们将因此，努力了解血管活性分子之间的这种转换及其对冠状动脉的影响变更。最后，我们将尝试通过以下方法改变肥厚型心肌病的内皮功能： 1-磷酸鞘氨醇类似物 FTY720，可防止早期建立的不可逆进展。