Inhibition of Prostaglandin E2Synthesis in Abdominal Aortic Aneurysms

• DOI: 10.1161/01.cir.100.1.48
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Lesley J. Walton; Ian J. Franklin; Trevor Bayston; Louise C. Brown; Roger M. Greenhalgh; Graham W. Taylor; Janet T. Powell
• Keywords: DNA Replication; Adolescent; Cyclooxygenase 2 Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Infant; Apoptosis; Dinoprostone; 3. Good health; Cohort Studies; 03 medical and health sciences; 0302 clinical medicine; Cyclooxygenase 2; Culture Media, Conditioned; Disease Progression; Humans; Cyclooxygenase Inhibitors; Female; Cell Division; Cells, Cultured; Chemokine CCL2; Aged; Aortic Aneurysm, Abdominal

Background —There is no treatment proven to limit the growth of abdominal aortic aneurysms, in which histological hallmarks include inflammation and medial atrophy, with apoptosis smooth muscle cells destruction elastin. Methods Results —Aneurysm biopsies were used for explant cultures, preparation cell isolation macrophages. Tissue macrophages stained strongly cyclooxygenase 2. Prostaglandin E 2 (PGE ) concentrations aneurysm tissue homogenates, conditioned medium from explants, isolated 49±22 ng/g, 319±38 ng/mL, 22±21 respectively. PGE inhibited DNA synthesis proliferation normal (IC 50 , 23.2±3.8 23.6±4.5 respectively). In derived aneurysmal aorta, also caused death, generation oligonucleosomes. Conditioned mixed monocyte cultures explants had potent growth-inhibitory effects, fractionation this showed that molecule(s) coeluted . indomethacin 10 μmol/L or mefenamic acid abolished secretion significantly reduced IL-1β IL-6 secretion. a separate case-control study, expansion aneurysms was compared 15 patients taking nonsteroidal anti-inflammatory drugs 63 control subjects; median rates 1.5 3.2 mm/y, respectively, P =0.001. Conclusions —The adverse effects on viability cytokine vitro apparent effect lower suggest selective inhibition could be an effective curtail expansion.