Monocyte activity is linked with abdominal aortic aneurysm diameter

Kiana M. Samadzadeh, Kevin C. Chun, Anthony T. Nguyen, Pamela M. Baker, Sukhmine Bains, Eugene S Lee

Research output: Contribution to journalArticle

16 Scopus citations

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. Materials and 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.

Original languageEnglish (US)
Pages (from-to)328-334
Number of pages7
JournalJournal of Surgical Research
Volume190
Issue number1
DOIs
StatePublished - 2014

Keywords

  • Abdominal aortic aneurysm
  • Adhesion
  • Inflammation
  • Matrix metalloproteinase
  • Monocytes
  • Transmigration

ASJC Scopus subject areas

  • Surgery

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