title: Characterization of circulating endothelial cells in acute myocardial infarction.
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.
authors.affiliation: Scripps Translational Science Institute, La Jolla, CA 92037, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: Damani
authors.forename: Andrea
authors.initials: A
authors.lastname: Bacconi
authors.forename: Ondrej
authors.initials: O
authors.lastname: Libiger
authors.forename: Aparajita H
authors.initials: AH
authors.lastname: Chourasia
authors.forename: Rod
authors.initials: R
authors.lastname: Serry
authors.forename: Raghava
authors.initials: R
authors.lastname: Gollapudi
authors.forename: Ron
authors.initials: R
authors.lastname: Goldberg
authors.forename: Kevin
authors.initials: K
authors.lastname: Rapeport
authors.forename: Sharon
authors.initials: S
authors.lastname: Haaser
authors.forename: Sarah
authors.initials: S
authors.lastname: Topol
authors.forename: Sharen
authors.initials: S
authors.lastname: Knowlton
authors.forename: Kelly
authors.initials: K
authors.lastname: Bethel
authors.forename: Peter
authors.initials: P
authors.lastname: Kuhn
authors.forename: Malcolm
authors.initials: M
authors.lastname: Wood
authors.forename: Bridget
authors.initials: B
authors.lastname: Carragher
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: John
authors.initials: J
authors.lastname: Jiang
authors.forename: Chandra
authors.initials: C
authors.lastname: Rao
authors.forename: Mark
authors.initials: M
authors.lastname: Connelly
authors.forename: Velia M
authors.initials: VM
authors.lastname: Fowler
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000293:injuries / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002452:Cell Count; D002465:Cell Movement; D002467:Cell Nucleus / Q000473:pathology; D048430:Cell Shape; D048429:Cell Size; D042783:Endothelial Cells / Q000166:cytology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009203:Myocardial Infarction / Q000473:pathology*; D009336:Necrosis; D010641:Phenotype
chemical_list: D015415:Biomarkers