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Characterization of circulating endothelial cells in acute myocardial infarction

Academic Article
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Overview

authors

  • Damani, S.
  • Bacconi, A.
  • Libiger, O.
  • Chourasia, A. H.
  • Serry, R.
  • Gollapudi, R.
  • Goldberg, R.
  • Rapeport, K.
  • Haaser, S.
  • Topol, S.
  • Knowlton, S.
  • Bethel, Kelly
  • Kuhn, Peter
  • Wood, Malcolm R.
  • Carragher, Bridget
  • Schork, Nicholas
  • Jiang, J.
  • Rao, C.
  • Connelly, M.
  • Fowler, Velia
  • Topol, Eric

publication date

  • 2012

journal

  • Science Translational Medicine  Journal

abstract

  • 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.

subject areas

  • Adult
  • Aged
  • Aged, 80 and over
  • Arteries
  • Biomarkers
  • Case-Control Studies
  • Cell Count
  • Cell Movement
  • Cell Nucleus
  • Cell Shape
  • Cell Size
  • Endothelial Cells
  • Female
  • Humans
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Myocardial Infarction
  • Necrosis
  • Phenotype
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Identity

PubMed Central ID

  • PMC3589570

International Standard Serial Number (ISSN)

  • 1946-6234

Digital Object Identifier (DOI)

  • 10.1126/scitranslmed.3003451

PubMed ID

  • 22440735
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Additional Document Info

start page

  • 126ra33

volume

  • 4

issue

  • 126

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