Characterization of Circulating Endothelial Cells in Acute Myocardial Infarction

被引:61
作者
Damani, Samir [1 ]
Bacconi, Andrea [2 ]
Libiger, Ondrej [1 ,2 ]
Chourasia, Aparajita H. [3 ]
Serry, Rod [4 ]
Gollapudi, Raghava [5 ,6 ]
Goldberg, Ron [5 ,6 ]
Rapeport, Kevin [5 ,6 ]
Haaser, Sharon [1 ]
Topol, Sarah [1 ]
Knowlton, Sharen [1 ]
Bethel, Kelly [2 ]
Kuhn, Peter [2 ]
Wood, Malcolm [2 ]
Carragher, Bridget [2 ]
Schork, Nicholas J. [1 ,2 ]
Jiang, John [3 ]
Rao, Chandra [3 ]
Connelly, Mark [3 ]
Fowler, Velia M. [2 ]
Topol, Eric J. [1 ,2 ]
机构
[1] Scripps Translat Sci Inst, La Jolla, CA 92037 USA
[2] Scripps Res Inst, La Jolla, CA 92037 USA
[3] Veridex LLC, Huntingdon Valley, PA 19006 USA
[4] Palomar Pomerado Hlth, Escondido, CA 92025 USA
[5] Sharp Mem Hosp & Rehabil Ctr, San Diego, CA 92123 USA
[6] Grossmont Hosp, San Diego, CA 92123 USA
关键词
DISEASE; ATHEROSCLEROSIS; RISK;
D O I
10.1126/scitranslmed.3003451
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Acute myocardial infarction (MI), which involves the rupture of existing atheromatous plaque, remains highly unpredictable despite recent advances in the diagnosis and treatment of coronary artery disease. Accordingly, a clinical measurement that can predict an impending MI is desperately needed. Here, we characterize circulating endothelial cells (CECs) using an automated and clinically feasible CEC three-channel fluorescence microscopy assay in 50 consecutive patients with ST-segment elevation MI and 44 consecutive healthy controls. CEC counts were significantly elevated in MI cases versus controls, with median numbers of 19 and 4 cells/ml, respectively (P = 1.1 x 10(-10)). A receiver-operating characteristic (ROC) curve analysis demonstrated an area under the ROC curve of 0.95, suggesting near-dichotomization of MI cases versus controls. We observed no correlation between CECs and typical markers of myocardial necrosis (rho = 0.02, creatine kinase-myocardial band; r = -0.03, troponin). Morphological analysis of the microscopy images of CECs revealed a 2.5-fold increase (P < 0.0001) in cellular area and a twofold increase (P < 0.0001) in nuclear area of MI CECs versus healthy controls, age-matched CECs, as well as CECs obtained from patients with preexisting peripheral vascular disease. The distribution of CEC images that contained from 2 to 10 nuclei demonstrates that MI patients were the only subject group to contain more than 3 nuclei per image, indicating that multicellular and multinuclear clusters are specific for acute MI. These data indicate that CEC counts may serve as a promising clinical measure for the prediction of atherosclerotic plaque rupture events.
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页数:9
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