Monocyte activity is linked with abdominal aortic aneurysm diameter

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 (R-2 = 0.66) and transmigratory (R-2 = 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. Published by Elsevier Inc.