Abstract 6050: Treatmeant with Rosuvastatin Suppresses the Development of Experimental Abdominal Aortic Aneurysms in Mice by Heme Oxygenase-1 Induction
Objective: Several authors have reported potential beneficial effects of statins in reducing abdominal aortic aneurysm (AAA) expansion in a manner independent of its cholesterol-lowering mechanism. We previously demonstrated that statins induce heme oxygenase-1 (HO-1) expression and, as a consequence, reduce oxidative stress in vascular cells. The purpose of this study was to assess the effect of statins on the progression of AAA expansion.
Method: Angiotensin II (1.0 mg/kg/min) was infused into 8-wk-old male ApoE−/− mice for 2 wks via osmotic minipumps. The mice were treated with daily IP injections of vehicle (n=8) or rosuvastatin (n=10) at dose of 5 mg/kg/d for 5 wks starting 3 wks prior to pump implantation. At the end of Angiotensin II (Ang II) infusion, suprarenal and infrarenal aortic diameters were measured by post mortem measurement. AAA severities were scored as 1 (having a suprarenal/infrarenal aortic diameter ratio under 2); 2 (diameter ratio over 2); or 3 (presence of dissection). HO enzyme activity in AAA was determined by gas chromatography.
Results: Rosuvastatin treatment did not significantly affect either body weight gain or plasma total cholesterol and triglyceride levels. Progression and severity of AAA expansion were higher in vehicle-treated mice compared to rosuvastatin-treated mice (2.29 ± 0.17 vs. 1.56 ± 0.23, p<0.05). Overall HO enzyme activity was not significantly different between groups (vehicle: 42.6±7.10 vs. rosuvastatin:51.2 ± 6.04 pmol CO/h/mg FW). But when categorized by AAA severity, HO activity in type 2 expansion was significantly higher after rosuvastatin treatment (31.0 ± 3.43 vs. 58.1± 9.00 pmol CO/hr/mg FW, p<0.05).
Conclusion: We conclude that rosuvastatin inhibits the progression of AAA expansion through the induction of HO activity. Development of specific targeted therapies that induce HO-1 may be a new therapeutic strategy for the prevention of AAA disease.