Assessing Circulating Progenitor Cells in Heart Disease

描述(由申请人提供)： 循环中能够修复血管的成体祖细胞的发现改变了我们对动脉粥样硬化的概念，从一种不可抗拒的进行性疾病转变为一种血管损伤和修复之间的平衡。CPC的数量已经与动脉粥样硬化的危险因素、冠状动脉疾病的程度和临床结果相关；然而，外周血样本中CPC的测量仍然很困难。已经报道了多种方法和技术来枚举CPC，但研究之间的一致性很小。我们建议使用前面描述的一种检测方法来研究接受心导管术的患者中的CPC数量，该方法基于细胞表面CD133和CD34的表达，CD13和VEGFR-2的表达，CD13和VEGFR-2的表达，并将这些祖细胞与乙醛脱氢酶(ALDH)活性测定所鉴定的那些细胞进行比较。我们将严格评估这两种检测方法的重复性和精密度。然后，我们将确定使用每种技术计数的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，我们将研究每种技术在冠状动脉旁路移植患者中使用的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点以及确定每种测试与临床因素的相关性，这项工作将描述CPC评估在预测预后中的作用。我们在CABG患者中的研究将首次不仅与基线直接相关，而且还将动员的CPC水平与骨髓祖细胞含量直接相关，并将为研究祖细胞耗竭的机制提供重要的见解。能够修复血管的成人干细胞的丧失可能是心脏病发展的一种解释。这项研究将考察两种测量心脏病患者血液中这些干细胞的方法。这些方法有朝一日可能被用来预测谁会或不会患上心脏病或其他并发症。

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.