Kiana M Samadzadeh1, Kevin C Chun1, Anthony T Nguyen1, Pamela M Baker1, Sukhmine Bains2, Eugene S Lee3. 1. Department of Research, Sacramento VA Medical Center, Mather, California. 2. Department of Surgery, Sacramento VA Medical Center, Mather, California; Department of Surgery, University of California, Sacramento, California. 3. Department of Surgery, Sacramento VA Medical Center, Mather, California; Department of Surgery, University of California, Sacramento, California. Electronic address: eugene.lee01@va.gov.
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. Published by Elsevier Inc.
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. Published by Elsevier Inc.
Authors: Jorn P Meekel; Menno E Groeneveld; Natalija Bogunovic; Niels Keekstra; René J P Musters; Behrouz Zandieh-Doulabi; Gerard Pals; Dimitra Micha; Hans W M Niessen; Arno M Wiersema; Jur K Kievit; Arjan W J Hoksbergen; Willem Wisselink; Jan D Blankensteijn; Kak K Yeung Journal: Sci Rep Date: 2018-05-25 Impact factor: 4.379