Assessing Circulating Progenitor Cells in Heart Disease

评估心脏病中的循环祖细胞

• 批准号: 7262498
• 负责人: Thomas Joseph Povsic
• 金额: $ 15.31万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-24 至 2008-12-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7262498
• 关键词: Adult; Adverse event; Age; Age Factors; Agreement; Aldehyde dehydrogenase (NAD+); Alkylating Agents; Atherosclerosis; Behavior; Biological Assay; Blood; Blood Vessels; Blood specimen; Bone Marrow; CD14 gene; CD34 gene; CD34+ precursor; Cardiac; Cardiac Catheterization Procedures; Cell Count; Cell physiology; Cell surface; Cells; Characteristics; Chronic; Clinical; Colony-forming units; Conceptions; Condition; Conflict (Psychology); Coronary Arteriosclerosis; Coronary Artery Bypass; Coronary heart disease; Count; Cultured Cells; Databases; Development; Diabetes Mellitus; Endothelial Cells; Engraftment; Equilibrium; Event; Experimental Models; Facility Construction Funding Category; Flow Cytometry; Future; Heart; Heart Diseases; Hematopoietic; Hematopoietic stem cells; Injury; Investigation; Lectin; Maintenance; Measurement; Measures; Methodology; Methods; Numbers; Outcome; PECAM1 gene; Patients; Performance; Peripheral; Plague; Process; Progressive Disease; Property; Purpose; Rate; Reporting; Reproducibility; Resistance; Risk Factors; Role; Staging; Staining method; Stains; Stem cells; Techniques; Testing; Time; Umbilical Cord Blood; Vascular Diseases; Vascular Endothelial Growth Factor Receptor-2; Work; adult stem cell; alanine aminopeptidase; aldehyde dehydrogenases; base; cell type; disorder risk; insight; novel; peripheral blood; progenitor; prognostic; reconstitution; repaired; response; vasculogenesis; volunteer

DESCRIPTION (provided by applicant): The discovery of circulating adult progenitor cells (CPCs) capable of vascular repair has altered our conception of atherosclerosis from an inexorably progressive disease to one represented by a balance between vascular damage and repair. The numbers of CPCs has been correlated with risk factors for atherosclerosis, the extent of coronary artery disease, and with clinical outcomes; nonetheless, the measurement of CPCs in peripheral blood samples remains difficult. Multiple assays and techniques for enumerating CPCs have been reported, with minimal agreement between studies. We propose to investigate the numbers of CPCs in patients undergoing cardiac catheterization using a previously described assays based on cell surface expression of CD 133 and CD34, representative of late outgrowth endothelial progenitors, expression of CD13 and VEGFR-2, representative of early endothelial progenitors, and compare these progenitors with those identified using an assay of aldehyde dehydrogenase (ALDH) activity. We will rigorously assess the reproducibility and precision of both assays. We will then determine the correlation between CPCs enumerated using each technique with cardiac risk factors, extent of coronary disease, and clinical outcomes. Finally, we will study CPC mobilization using each technique in patients undergoing coronary artery bypass grafting, and compare CPC numbers and CPC mobilization with bone marrow progenitor cell content. By delineating the performance characteristics of these tests as well as determining the correlation of each with clinical factors, this work will delineate the role of CPC assessment for prognostic purposes. Our study in CABG patients will be the first to directly correlate not only baseline, but mobilized CPC levels with bone marrow progenitor cell content, and will offer important insights into mechanisms of progenitor cell depletion. Loss of adult stem cells capable of repairing blood vessels may be one explanation for the development of heart disease. This study will look at two methods of measuring these stem cells in the blood of heart patients. These methods may someday be used to predict who will or will not develop heart disease or other complications.

描述（由申请人提供）： 具有血管修复能力的循环成体祖细胞（CPC）的发现改变了我们对动脉粥样硬化的概念，从一种不可阻挡的进展性疾病转变为一种以血管损伤与修复之间的平衡为代表的疾病。 CPC 的数量与动脉粥样硬化的危险因素、冠状动脉疾病的程度以及临床结果相关。然而，外周血样本中 CPC 的测量仍然很困难。已有多种 CPC 计数分析方法和技术被报道，但研究之间的一致性极低。我们建议使用先前描述的基于 CD 133 和 CD34（代表晚期生长内皮祖细胞）的细胞表面表达、CD13 和 VEGFR-2（代表早期内皮祖细胞）的表达、并将这些祖细胞与通过乙醛脱氢酶 (ALDH) 活性测定鉴定的祖细胞进行比较。我们将严格评估这两种检测的重现性和精确度。然后，我们将确定使用每种技术计算的 CPC 与心脏危险因素、冠状动脉疾病程度和临床结果之间的相关性。最后，我们将研究接受冠状动脉旁路移植术的患者使用每种技术的 CPC 动员，并将 CPC 数量和 CPC 动员与骨髓祖细胞含量进行比较。通过描述这些测试的性能特征以及确定每个测试与临床因素的相关性，这项工作将描述 CPC 评估在预后方面的作用。我们对 CABG 患者的研究将是第一个不仅将基线水平而且动员的 CPC 水平与骨髓祖细胞含量直接相关的研究，并将为祖细胞耗竭机制提供重要的见解。能够修复血管的成体干细胞的丧失可能是心脏病发生的一种解释。这项研究将探讨两种测量心脏病患者血液中干细胞的方法。这些方法有一天可能会被用来预测谁会或不会患心脏病或其他并发症。

项目成果

The effect of aspirin on endothelial progenitor cell biology: preliminary investigation of novel properties.

阿司匹林对内皮祖细胞生物学的影响：新特性的初步研究。

• DOI: 10.1016/j.thromres.2009.11.017
• 发表时间: 2010
• 期刊: Thrombosis research
• 影响因子: 7.5
• 作者: Lou,Junyang;Povsic,ThomasJ;Allen,JasonD;Adams,StacieD;Myles,Shelley;Starr,AijingZ;Ortel,ThomasL;Becker,RichardC
• 通讯作者: Becker,RichardC