PROJECT
1. Differential expression of prostaglandin E-2 and interleukin-6 in occlusive and aneurysmal aortic disease Reilly JM, Miralles K, Wester WN, Sicard GA SURGERY 126: (4) 624-627 OCT 1999 Abstract: Background. Both aortoiliac occlusive disease (AIOD) and abdominal aortic aneurysm disease (AAA) are traditionally considered degenerative conditions that are caused by athersclerosis. Although it is becoming apparent that the pathophysiology of each condition has its own determinants, inflammation is thought to play a role in each. The purpose of this study was to analyze the inflammatory cytokines interleukin-6 (IL-6) and prostaglandin E-2 (PGE2) in aortic disease and compare AAA with AIOD, as well as to compare both with normal aorta. Methods. Aortic tissue was harvested at the time of aortic reconstructive surgery for AAA (n = 13) and AIOD (n = 14) or at time of organ harvest for normal (n = 16) aortic specimens. Whole organ cultures were immediately established, and the culture medium was collected after 72 hours. An enzyme-linked immunosorbent assay was used to assay for PCE2 and a lymphoproliferative assay was used to quantitate IL-6. Statistical analysis was performed using paired 2-tail t tests. Results. Normal aorta expressed much less PGE2 (384 +/- 67 ng/mL) than either AAA (11, 093 +/- 7, 411 ng/mL) (P <.001) or AIOD (13,719 +/- 3,355 ng/mL) (P <.002). However, there was no statistically significant difference in PGE2 expression between the AAA and AIOD groups (P =.44). The IL-6 assay also showed that normal aorta had very little expression (1,861 +/- 334 U/mL) compared with either AAA (14,329 +/- 4,159 U/mL) (P =.02) or AIOD (39,805 +/- 8,426) (P <.001). Comparison between AAA and AIOD revealed significantly higher expression of IL-6 by the AIOD cultures (P =.03). Conclusions. AAA and AIOD are associated with increased expression of the proinflammatory cytokines PGE2 and IL-6. However AIOD is associated with a much higher level of IL-6 expression than is AAA, although the level of PGE2 ex;expression is the same. This differential expression of IL-6 may hell, explain the pathogenesis of these 2 distinct aortic diseases. Comment by mdt: This paper by Reilly et al serves as an introduction to the following offering from the Charing Cross group. 2. Inhibition of prostaglandin E-2 synthesis in abdominal aortic aneurysms - Implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms Walton LJ, Franklin IJ, Bayston T, Brown LC, Greenhalgh RM, Taylor GW, Powell JT CIRCULATION 100: (1) 48-54 JUL 6 1999 Abstract: Background-There is no treatment proven to limit the growth of abdominal aortic aneurysms, in which the histological hallmarks include inflammation and medial atrophy, with apoptosis of smooth muscle cells and destruction of elastin. Methods and Results-Aneurysm biopsies were used for explant cultures, the preparation of smooth muscle cell cultures, and isolation of macrophages. Tissue macrophages stained strongly for cyclooxygenase 2. Prostaglandin E-2 (PGE(2)) concentrations in aneurysm tissue homogenates, conditioned medium from explants, and isolated macrophages were 49 +/- 22 ng/g, 319 +/- 38 ng/mL, and 22 +/- 21 ng/mL, respectively. PGE(2) inhibited DNA synthesis and proliferation in normal aortic smooth muscle cells (IC50, 23.2 +/- 3.8 and 23.6 +/- 4.5 ng/mL, respectively). In smooth muscle cells derived from aneurysmal aorta, PGE(2) also caused cell death, with generation of oligonucleosomes. Conditioned medium from the mixed smooth muscle and monocyte cultures derived from explants also had potent growth-inhibitory effects, and fractionation of this medium showed that the growth-inhibitory molecule(s) coeluted with PGE(2). In explants, indomethacin 10 mu mol/L or mefenamic acid 10 mu mol/L abolished PGE(2) secretion and significantly reduced LL-1 beta and IL-6 secretion. In a separate case-control study, the expansion of abdominal aortic aneurysms was compared in 15 patients taking nonsteroidal anti-inflammatory drugs and 63 control subjects; median growth rates were 1.5 and 3.2 mm/y, respectively, P = 0.001. Conclusions The adverse effects of PGE(2) on aortic smooth muscle cell viability and cytokine secretion in vitro and the apparent effect of anti-inflammatory drugs to lower aneurysm growth rates suggest that selective inhibition of PGE(2) synthesis could be an effective treatment to curtail aneurysm expansion. Comment by mdt: In fact, in another study (Br J Surg 1999; 86: 707), the Charing Cross group reports that the median growth rate of 19 patients taking non- steroidal anti-inflammatory drugs was 1.8 mm/yr; versus 3.2 mm/yr in controls. This is an impressive finding. 3. Prevalence of abdominal aortic aneurysms in urology patients referred for ultrasound Davies AJ, Winter RK, Lewis MH ANNALS OF THE ROYAL COLLEGE OF SURGEONS OF ENGLAND 81: (4) 235-238 JUL 1999 Abstract: During a 3-year period, all urology patients over the age of 50 years referred for ultrasound investigation of the renal tract, underwent routine examination of the abdominal aorta. A total of 2281 patients were examined (1798 men and 483 women) and an abdominal aortic aneurysm was detected in 57 (2.5%). In men over the age of 65 years, 47 aneurysms were detected (4.9%). The mean time taken to scan the aorta was 43 s. We recommend the routine practice of examining the abdominal aorta in all men over the age of 60 years referred for ultrasound examination of the renal tract. Comment by mdt: Good idea!