title: Osteogenic monocytes within the coronary circulation and their association with plaque vulnerability in patients with early atherosclerosis.
abstract: OBJECTIVE
  This study tests the hypothesis that circulating mononuclear cells expressing osteocalcin (OCN) and bone alkaline phosphatase (BAP) are associated with distinct plaque tissue components in patients with early coronary atherosclerosis.
  
  
  BACKGROUND
  Plaque characteristics implying vulnerability develop at the earliest stage of coronary atherosclerosis. Increasing evidence indicates that cells from the myeloid lineage might serve as important mediators of destabilization. Plaque burden and its components were assessed regarding their relationship to monocytes carrying both pro-inflammatory (CD14) and osteogenic surface markers OCN and BAP.
  
  
  METHODS
  Twenty-three patients with angiographically non-obstructive coronary artery disease underwent coronary endothelial function assessment and virtual histology-intravascular ultrasound of the left coronary artery. Plaque composition was characterized in the total segment (TS) and in the target lesion (TL) containing the highest amount of plaque burden. Blood samples were collected simultaneously from the aorta and the coronary sinus. Circulating cell counts were then identified from each sample and a gradient across the coronary circulation was determined.
  
  
  RESULTS
  Circulating CD14+/BAP+/OCN+ monocytes correlate with the extent of necrotic core and calcification (r=0.53, p=0.010; r=0.55, p=0.006, respectively). Importantly, coronary retention of CD14+/OCN+ cells also correlates with the amount of necrotic core and calcification (r=0.61, p=0.003; r=0.61, p=0.003) respectively.
  
  
  CONCLUSIONS
  Our study links CD14+/BAP+/OCN+ monocytes to the pathologic remodeling of the coronary circulation and therefore associates these cells with plaque destabilization in patients with early coronary atherosclerosis.
authors.affiliation: Department of Cardiology, West-German Heart-Center - University Hospital Essen, Essen, Germany; Department of Internal Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Collin
authors.affiliation: Department of Cardiology, Dean Clinic - Dean St. Mary's Outpatient Hospital Center, Madison, WI, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Gössl
authors.affiliation: Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Matsuo
authors.affiliation: Divison of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Cilluffo
authors.affiliation: Department of Cardiology, University Hospital of Zurich, Zurich, Switzerland.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Flammer
authors.affiliation: Divison of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: Darrell
authors.initials: D
authors.lastname: Loeffler
authors.affiliation: Division of Biomedical Statistics and Informatics, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Lennon
authors.affiliation: Department of Internal Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Simari
authors.affiliation: Divison of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Spoon
authors.affiliation: Department of Cardiology, West-German Heart-Center - University Hospital Essen, Essen, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
authors.affiliation: Division of Endocrinology, Mayo Clinic, College of Medicine, Rochester, MN, USA.
authors.forename: Sundeep
authors.initials: S
authors.lastname: Khosla
authors.affiliation: Divison of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, College of Medicine, Rochester, MN, USA. Electronic address: lerman.amir@mayo.edu.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D003326:Coronary Circulation; D005260:Female; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood*; D062072:Patient Acuity; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013223:Statistics as Topic; D018084:Ultrasonography, Interventional / Q000379:methods
chemical_list: D018950:Lipopolysaccharide Receptors; D015675:Osteocalcin; D000469:Alkaline Phosphatase
keywords: Atherosclerosis; Blood cells; Imaging; Vulnerable plaque