Characterization of Circulating Endothelial Cells in Acute Myocardial Infarction

Autor: Eric J. Topol, Aparajita H. Chourasia, Kelly Bethel, Andrea Bacconi, Chandra Rao, Rod Serry, Ondrej Libiger, Samir Damani, Bridget Carragher, Peter Kuhn, Sharon Haaser, Sharen Knowlton, Raghava R. Gollapudi, Malcolm R. Wood, Ron Goldberg, John Jiang, Velia M. Fowler, Nicholas J. Schork, Mark Connelly, Kevin Rapeport, Sarah E. Topol
Rok vydání: 2012
Předmět:
Zdroj: Science Translational Medicine. 4
ISSN: 1946-6242
1946-6234
DOI: 10.1126/scitranslmed.3003451
Popis: 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 × 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 (ρ = 0.02, creatine kinase-myocardial band; ρ = -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.
Databáze: OpenAIRE