Vascular smooth muscle cell heterogeneity and disease

血管平滑肌细胞异质性与疾病

基本信息

批准号：
10356855
负责人：
Michael Simons
金额：
$ 83.06万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2024-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10356855
关键词：
Abdominal Aortic Aneurysm Adipocytes Aneurysm Aorta Arterial Fatty Streak Atherosclerosis Blood Vessels Bone Marrow Cardiovascular system Cartilage Cells Cerebrum Characteristics Chest Chronic Clonal Expansion Clone Cells Coronary artery Cytometry Data Development Dilatation - action Disease Endothelial Cells Endothelium Exhibits Genetic Genetic Transcription Goals Health Heterogeneity Human Image Inflammation Link Lung Medial Mesenchymal Mesenchymal Stem Cells Minority Molecular Molecular Analysis Mononuclear Mus Myocardial Infarction Organ Donor Paint Pathogenesis Pathogenicity Pathologic Pathology Peripheral Vascular Diseases Phenotype Physiologic Ossification Population Process Pulmonary Hypertension Reporting Signal Transduction Site Smooth Muscle Smooth Muscle Myocytes Stroke Therapeutic Time Time Series Analysis Vascular Diseases Vascular Smooth Muscle bone calcification cell type cerebral cavernous malformations fascinate human disease macrophage mouse model novel therapeutics pathogen pulmonary arterial hypertension response single-cell RNA sequencing stem-like cell tool

项目摘要

Project Summary Vascular cell heterogeneity is a fascinating but poorly understood phenomenon. Numerous vascular cell types undergo fate transitions under pathological conditions. This includes endothelial cells (ECs) undergoing endothelial-to-mesenchymal transition (EndMT) and acquiring certain characteristics typical of macrophages and smooth muscle cells (SMCs). SMCs, in turn, can also acquire macrophage-like features while bone marrow-derived mononuclear cells can express certain EC and SMC markers when present at sites of chronic inflammation. These cells fate transitions have been linked to various pathologies including atherosclerosis, aneurysms, pulmonary hypertension and cavernous cerebral malformations. While the existence of these cell fate transitions is now well accepted, little is known about the origin and characteristics of SMCs undergoing these fate changes. Our preliminary data suggest that certain subpopulations of normal SMCs are particularly prone to phenotypic modulation and are predominately pathogenic. We hypothesize that a small subpopulation of normal SMCs is responsible for pathogenesis of CV diseases associated with expansion of the SMC pool and that targeting these cells might prove to be a better and more specific therapeutic approach. It is our goal in this application to define these cell populations, determine what drives their pathogenic responses and begin identifying therapeutic approaches to controlling CV illnesses driven by specifically targeting these SMC subsets.

项目概要血管细胞异质性是一个令人着迷但人们知之甚少的现象。血管细胞众多类型在病理条件下经历命运转变。这包括内皮细胞 (EC) 内皮-间质转化（EndMT）并获得巨噬细胞的某些典型特征和平滑肌细胞（SMC）。反过来，SMC 也可以获得巨噬细胞样特征，而骨当存在于慢性病部位时，骨髓来源的单核细胞可以表达某些 EC 和 SMC 标记物。炎。这些细胞的命运转变与多种病理学有关，包括动脉粥样硬化、动脉瘤、肺动脉高压和海绵状脑畸形。虽然这些细胞的存在命运转变现在已被广泛接受，但人们对经历命运转变的 SMC 的起源和特征知之甚少。这些命运的改变。我们的初步数据表明，正常 SMC 的某些亚群特别易于表型调节并且主要是致病性的。我们假设一小部分人群正常 SMC 的减少是与 SMC 池扩张相关的 CV 疾病的发病机制的原因并且针对这些细胞可能被证明是一种更好、更具体的治疗方法。这是我们的目标在此应用中定义这些细胞群，确定驱动其致病反应的因素并开始确定专门针对这些 SMC 驱动的控制心血管疾病的治疗方法子集。