Abstract 514: Cilostazol Attenuated Angiotensin II-induced Abdominal Aortic Aneurysms Thorough Anti-inflammatory Effect in Apolipoprotein E-deficient Mice
Objective Chronic angiotensin II (AngII) infusion promotes development of abdominal aortic aneurysms (AAAs) in mice. Previous studies have shown that local inflammation plays an important role on formation of AAAs. Cilostazol, a phosphodiesterase-3 inhibitor with antiplatelet aggregation and vasodilatory effects, exerts vasoprotective effect by inhibiting inflammation and superoxide generation in several experimental studies. The purpose of this study was to evaluate whether cilostazol influenced AngII-induced AAAs.
Methods and Results Male apolipoprotein E deficient mice (8-12 weeks old) were fed with either normal diet or cilostazol-containing (0.1% wt/v) diet. After 1 week of cilostazol administration, mice were infused subcutaneously with either AngII (1,000 ng/kg/min, n = 16 -19) or saline (n = 5 - 6) by osmotic minipumps for 4 weeks. AngII equivalently increased systolic blood pressure, irrespective of cilostazol administration. Cilostazol had no effect on serum cholesterol concentrations, triglycerides, high-density lipoprotein-cholesterol, body weights, heart rates, and systolic blood pressures. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas that were attenuated by cilostazol administration (1.94 ± 0.16 mm vs 1.53 ± 0.17 mm, P < 0.05). Cilostazol diminished AngII-induced increase of aortic MMP-2 activity and ICAM-1 protein expression as determined by gelatin zymography and Western blot, respectively (P < 0.05, each). Aortic mRNA expression of inflammatory cytokines such as MCP-1, IL-1β, osteopontin, and COX-2 was reduced by cilostazol administration (P < 0.05). In vitro, TNF-α increased MCP-1, ICAM-1 and VCAM-1 mRNA expression in mouse aortic endothelial cells. These enhancements were decreased by incubation with cilostazol (P < 0.05).
Conclusion Cilostazol attenuated AngII-induced AAAs thorough its anti-inflammatory effect in male apolipoprotein E deficient mice.
- © 2013 by American Heart Association, Inc.