Angiogenesis Inhibitors Endostatin or TNP-470 Reduce Intimal Neovascularization and Plaque Growth in Apolipoprotein E–Deficient Mice

• DOI: 10.1161/01.cir.99.13.1726
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Karen S. Moulton; Eric Heller; Moritz A. Konerding; Evelyn Flynn; Wulf Palinski; Judah Folkman
• Keywords: Endostatin; Apolipoprotein E

Background —Neovascularization within the intima of human atherosclerotic lesions is well described, but its role in progression atherosclerosis unknown. In this report, we first demonstrate that intimal vessels occur advanced apolipoprotein E–deficient (apoE −/−) mice. To test hypothesis promote atherosclerosis, investigated effect angiogenesis inhibitors on plaque growth apoE −/− Methods and Results —ApoE mice were fed a 0.15% cholesterol diet. At age 20 weeks, divided into 3 groups treated for 16 weeks as follows: group 1, recombinant mouse endostatin, mg · kg −1 d ; 2, fumagillin analogue TNP-470, 30 mg/kg every other day; 3, control animals received similar volume buffer. Average levels all groups. Plaque areas quantified at aortic origin. Median area before treatment was 0.250 mm 2 (range, 0.170 to 0.348; n=10). 0.321 (0.238 0.412; n=10), 0.402 (0.248 0.533; n=15), 0.751 (0.503 0.838; n=12) groups, respectively ( P ≤0.0001). Therefore, endostatin TNP-470 inhibited during period by 85% 70%. Intimal smooth muscle cell contents plaques from similar. Conclusions —Prolonged with either inhibitor reduced neovascularization Although mechanism inhibition induced these agents not established, results suggest may development.