Effects of Caspase Inhibitor on Angiotensin II-Induced Abdominal Aortic Aneurysm in Apolipoprotein E–Deficient Mice

Objective— The presence of apoptotic markers is a prominent histological feature of abdominal aortic aneurysm. To understand the role of apoptosis in the pathogenesis of this common vascular disease, we tested the effect of the pan-caspase inhibitor quinoline-Val-Asp-difluorophenoxymethylketone (Q-Vd-OPh) on aneurysm formation using a mouse angiotensin II (Ang II) model. Methods and Results— Ang II in apolipoprotein E–deficient mice significantly induced medial cell apoptosis 3 days after infusion at the aortic region, eventually becoming aneurismal. A daily administration of 20 mg/kg per day Q-Vd-OPh starting 6 hours before Ang II infusion reduced aneurysm incidence from 83.3% to 16.7% and maximal aortic diameter from 2.43±0.29 mm to 1.58±0.18 mm. The caspase inhibitor treated mice showed profoundly diminished levels of medial apoptosis and inflammation. In contrast, administration of Q-Vd-OPh starting 7 days after Ang II infusion had no significant impact on aneurysm development. In vitro, media conditi...