Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Vascular surgical society of great britain and ireland: non-steroidal anti-inflammatory drugs to treat abdominal aortic aneurysm 1036 45

The rat model of abdominal aortic aneurysm (AAA) is associated with inflammation, destruction of extracellular matrix, and production of both inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-9 (MMP-9). Indomethacin, a nonselective cyclooxygenase inhibitor, may prevent AAA formation by inhibiting cyclooxygenase-2 (COX-2) activity. We hypothesized that indomethacin, rofecoxib (selective COX-2 inhibitor), and 1400 W (selective iNOS activity inhibitor) would decrease aneurysm formation in the rat model. Forty-six male Wistar rats underwent intraaortic elastase infusion in two parallel studies based on medication delivery route. Sixteen rats were randomized to rofecoxib or water by gastric lavage. Thirty rats were randomized to subcutaneous saline, indomethacin, or 1400 W. Heart rate, blood pressure and aortic diameters were measured. Western Blot and mRNA analysis for MMP-9 and iNOS was performed on postoperative day 7 aortic segments. Elastin degradation and inflammation were evaluated by immunohistochemistry. Elastase infusion produced AAA in all rats. 1400 W significantly limited aneurysm expansion (p = 0.01) whereas treatment with indomethacin and rofecoxib did not. Only 1400 W significantly increased blood pressure (p < 0.001). Indomethacin alone statistically decreased MMP-9 (p < 0.011). 1400 W resulted in greater conservation of aortic elastin than indomethacin (p = 0.025). All groups demonstrated statistically similar expression of iNOS. In conclusion, selective iNOS activity inhibitor, 1400 W, significantly decreased aneurysm size and preserved aortic elastin without altering MMP-9 levels. Indomethacin significantly decreased MMP-9 expression without decreasing aneurysm size. Rofecoxib did not significantly decrease MMP-9 expression or aneurysm size. Inhibition of iNOS limits aneurysmal expansion by mechanisms other than MMP-9 inhibition. MMP-9 inhibition by indomethacin is not sufficient to limit aneurysm expansion in our model.
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PMID:Suppression of experimental aortic aneurysms: comparison of inducible nitric oxide synthase and cyclooxygenase inhibitors. 1577 Mar 65