Walton, LJ, Franklin, IJ, Bayston, T, Brown, LC, Greenhalgh, RM, Taylor, GW & Powell, JT 1999, 'Inhibition of Prostaglandin E 2 Synthesis in Abdominal Aortic Aneurysms', Circulation, vol. 100, no. 1, pp. 48-54.
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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 (IC 50 , 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 μmol/L or mefenamic acid 10 μmol/L abolished PGE 2 secretion and significantly reduced IL-1β 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,
Monnink, SHJ, Tio, RA, van Boven, AJ, van Geel, PP, Veeger, NJGM, de Kam, PJ, Pont, L & van Gilst, WH 1970, 'Angiotensin II receptor polymorphism is associated with endothelial function on top of other cardiovascular risk factors: The intervention cardiology risk stratification (ICARIS) study', CIRCULATION, LIPPINCOTT WILLIAMS & WILKINS, pp. 48-48.
