Abstract 17101: Prevention of Abdominal Aortic Aneurysms by Inhibition of Renin Activity in a Rabbit Model
Abdominal aortic aneurysm (AAA) is a common degenerative condition with high mortality in older men. However, there is no proven medical therapy to inhibit AAA progression in the clinical setting. Recent studies demonstrated that angiotensin II exerts direct effects on the arterial wall to influence aneurysm development with the induction of vascular inflammation. Therefore, we examined the hypothesis that inhibition of renin activity would decrease the expansion of abdominal aortic aneurysm in a rabbit model. Aortic dilatation was induced by incubation with elastase for 2 hours around the abdominal aorta in rabbits. A direct renin inhibitor, aliskiren, was given at doses of 10 mg/kg/day (n=15), via osmotic mini-pumps implanted, from operation to 4 weeks after operation. The aortic size was measured using ultrasonography before and after laparotomy once a week up to four weeks after operation. Treatment with aliskiren significantly decreased tissue renin activity in aneurysm wall as compared to control (n=5, p<0.05) at four weeks after administration. Ultrasound analysis demonstrated that the treatment with aliskiren significantly inhibited the expansion of experimental AAA (n=15, p<0.05), independent of its blood pressure-lowering effect. Moreover, treatment with aliskiren protected against destruction of elastic fibers. The therapeutic effects of aliskiren on AAA formation were associated with modification of transcriptional profile through inhibition of activity of multiple transcription factors, NFκB, AP-1 and CREB. As a result, treatment with aliskiren inhibited the activation of MMP-2 and MMP-9 (n=5, p<0.05), and suppression of macrophages accumulation (n=5, p<0.05) in aneurysm wall. The present study indicated that inhibition of renin activity using aliskiren could become a potent therapeutic option for hypertensive patients with AAA.
- © 2012 by American Heart Association, Inc.