Vascular surgical society of great britain and ireland: non-steroidal anti-inflammatory drugs to treat abdominal aortic aneurysm

• Published in: British journal of surgery 1999-05, Vol.86 (5), p.707-707
• Main Authors: Franklin, IJ, Walton, LJ, Brown, L, Greenhalgh, RN, Powell, JT
• Format: Article
• Language: English
• ISSN: 1365-2168

BACKGROUND: Prostaglandin E2 (PGE2) and inflammatory cytokine levels are raised in the wall of abdominal aortic aneurysms (AAAs) and inflammatory processes appear to contribute to aneurysm expansion. The effect of PGE2 on aortic smooth muscle cells (SMCs) and the influence of indomethacin on AAA growth and production of inflammatory mediators were investigated. METHODS: Proliferation and apoptosis of aortic SMCs cultured with PGE2 were assessed by 5-bromo-2'-deoxyuridine uptake and oligonucleosome enzyme-linked immunosorbent assay. Full-thickness AAA explant cultures were used to measure the secretion of PGE2, interleukin (IL) 1beta and IL-6 in the presence and absence of indomethacin. In a case-control study, the effect of non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin, on AAA growth was examined. RESULTS: PGE2 suppressed proliferation (IC50 6 ng ml-1) and increased apoptosis of aneurysm SMCs. Indomethacin diminished secretion of PGE2, IL-1beta and IL-6 by AAA explants (see Table below). The median AAA growth rate of 19 patients taking NSAIDs was 1.8 (range 0-11.2) mm per year compared with 3.2 (0.4-10.9) mm per year in 59 patients (matched for age, sex, smoking and initial AAA diameter) not taking these drugs (P = 0.004). CONCLUSION: PGE2 is produced in the AAA wall in concentrations that are detrimental to SMCs. Indomethacin reduces PGE2, IL-1beta and IL-6 synthesis in aneurysm tissue and NSAIDs appear to reduce AAA growth. These drugs warrant further consideration for the treatment of AAA.