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）： 能够进行血管修复的循环成人祖细胞（CPC）发现我们对动脉粥样硬化的概念从不可分割的渐进疾病变为由血管损伤和修复之间平衡的代表。 CPC的数量与动脉粥样硬化，冠状动脉疾病程度以及临床结局的危险因素有关。但是，外周血样本中CPC的测量仍然很困难。据报道，有关列举CPC的多种测定和技术，研究之间的一致性很小。我们建议研究基于CD 133和CD34的细胞表面表达的先前描述的测定的患者中的CPC数量，CD 133和CD34（代表后期生长的内皮祖细胞代表，CD13和VEGFR-2）的表达，代表早期内皮祖细胞的代表，并将这些祖先与这些祖先相比，将这些祖先与Alsy deledy的活动进行了比较。我们将严格评估这两种测定法的可重复性和精度。然后，我们将使用每种技术与心脏危险因素，冠状动脉疾病程度和临床结局进行列举的CPC之间的相关性。最后，我们将在接受冠状动脉搭桥术的患者中使用每种技术研究CPC动员，并将CPC数量和CPC动员与骨髓祖细胞细胞含量进行比较。通过描述这些测试的性能特征，并确定每个测试与临床因素的相关性，这项工作将描述CPC评估的作用，以预后目的。我们对CABG患者的研究将不仅直接与基线直接相关，而且将CPC水平与骨髓祖细胞细胞含量相关，并将为祖细胞耗竭机制提供重要的见解。能够修复血管的成年干细胞损失可能是心脏病发展的一种解释。这项研究将研究两种测量心脏血液中这些干细胞的方法。这些方法可能有一天可以用来预测谁将或不会发展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