title: Monocyte activity is linked with abdominal aortic aneurysm diameter.
abstract: BACKGROUND
  Systemic inflammation and increased matrix metalloproteinase (MMP) cause elastin degradation leading to abdominal aortic aneurysm (AAA) expansion. Several prospective studies report that statin therapy can reduce AAA expansion through anti-inflammation. We hypothesize that monocyte activity plays a pivotal role in this AAA development and this study examines patient peripheral blood monocyte cell adhesion, transendothelial migration, and MMP concentrations between AAA and non-AAA patients.
  
  
  METHODS
  Peripheral blood was collected and monocytes isolated from control (n=15) and AAA (n=13) patients. Monocyte adhesion, transmigration, and permeability assays were assessed. Luminex assays determined MMP-9 and tissue inhibitor of metalloproteinase-4 (TIMP-4) concentrations from cell culture supernatant and patient serum.
  
  
  RESULTS
  AAA patient monocytes showed increased adhesion to the endothelium relative fluorescence units (RFU, 0.33±0.17) versus controls (RFU, 0.13±0.04; P=0.005). Monocyte transmigration was also increased in AAA patients (RFU, 0.33±0.11) compared with controls (RFU, 0.25±0.04, P=0.01). Greater numbers of adhesive (R2=0.66) and transmigratory (R2=0.86) monocytes were directly proportional to the AAA diameter. Significantly higher serum levels of MMP-9 (2149.14±947 pg/mL) were found in AAA patients compared with controls (1189.2±293; P=0.01). TIMP-4 concentrations were significantly lower in AAA patients (826.7±100 pg/mL) compared with controls (1233±222 pg/mL; P=0.02). Cell culture supernatant concentrations of MMP and TIMP from cocultures were higher than monocyte-only cultures.
  
  
  CONCLUSIONS
  Monocytes from AAA patients have greater adhesion and transmigration through the endothelium in vitro, leading to elevated MMP-9 levels and the appropriate decrease in TIMP-4 levels. The ability to modulate monocyte activity may lead to novel medical therapies to decrease AAA expansion.
authors.affiliation: Department of Research, Sacramento VA Medical Center, Mather, California.
authors.forename: Kiana M
authors.initials: KM
authors.lastname: Samadzadeh
authors.affiliation: Department of Research, Sacramento VA Medical Center, Mather, California.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Chun
authors.affiliation: Department of Research, Sacramento VA Medical Center, Mather, California.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Nguyen
authors.affiliation: Department of Research, Sacramento VA Medical Center, Mather, California.
authors.forename: Pamela M
authors.initials: PM
authors.lastname: Baker
authors.affiliation: Department of Surgery, Sacramento VA Medical Center, Mather, California; Department of Surgery, University of California, Sacramento, California.
authors.forename: Sukhmine
authors.initials: S
authors.lastname: Bains
authors.affiliation: Department of Surgery, Sacramento VA Medical Center, Mather, California; Department of Surgery, University of California, Sacramento, California. Electronic address: eugene.lee01@va.gov.
authors.forename: Eugene S
authors.initials: ES
authors.lastname: Lee
mesh_terms: D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000473:pathology; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D020780:Matrix Metalloproteinase 9; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4
keywords: Abdominal aortic aneurysm; Adhesion; Inflammation; Matrix metalloproteinase; Monocytes; Transmigration