Assessing Circulating Progenitor Cells in Heart Disease

描述（由申请人提供）： 循环中具有血管修复能力的成体祖细胞（CPC）的发现改变了我们对动脉粥样硬化的认识，使其从一种不可阻挡的进展性疾病转变为一种以血管损伤和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。已报道了用于计数CPC的多种测定和技术，研究之间的一致性极小。我们建议使用先前描述的基于细胞表面CD 133和CD 34（代表晚期生长内皮祖细胞）表达、CD 13和VEGFR-2（代表早期内皮祖细胞）表达的测定法，研究接受心导管插入术的患者中CPC的数量，并将这些祖细胞与使用醛脱氢酶（ALDH）活性测定法鉴定的祖细胞进行比较。我们将严格评估这两种检测方法的重现性和精密度。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局之间的相关性。最后，我们将研究在接受冠状动脉旁路移植术的患者中使用每种技术的CPC动员，并比较CPC数量和CPC动员与骨髓祖细胞含量。通过描述这些测试的性能特征以及确定每个与临床因素的相关性，这项工作将描述CPC评估预后的作用。我们在CABG患者中的研究将是第一个不仅将基线，而且将动员的CPC水平与骨髓祖细胞含量直接相关的研究，并将为祖细胞耗竭的机制提供重要的见解。能够修复血管的成体干细胞的丢失可能是心脏病发展的一种解释。这项研究将着眼于测量心脏病患者血液中这些干细胞的两种方法。这些方法有一天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.