Abstract 455: Fimasartan Reduced Carotid Atherosclerosis Progression After Mechanical Injury in ApoE Knockout Mouse

Abstract

Aim: The beneficial effects of angiotensin receptor blockers (ARBs) in atherosclerosis have been demonstrated in numerous studies. We investigated the effects of fimasartan in reducing atherosclerosis progression and systemic inflammation after carotid artery injury in ApoE knockout mouse. Methods: Male ApoE knockout mice were randomly allocated to Group 1 (without carotid artery injury, n =20), Group 2 (without carotid artery injury + fimasartan, n =21), Group 3 (carotid artery injury, n =25) and Group 4 (carotid artery injury + fimasartan, n =24). Fimasartan (3mg/kg in distilled water) was orally injected on daily basis, and left carotid artery injury was induced with 0.014 inch guidewire. At 28 days, hematoxylin & eosin and elastic stains were used to measure cross-sectional atherosclerotic plaque from carotid artery. Moreover, inflammatory markers such as MMP9, IL-6, TNFα and ICAM were analyzed by ELISA, and anti-inflammatory cytokines such as IL-10 was measured in peripheral blood. Results: Histomorphometric staining showed significantly reduced neointimal hyperplasia in Group 2 (2.30±0.66%) compared to Group 1 (12.31±2.97%, p <0.05). In addition, Group 4 (32.03±4.62%) showed significantly reduced neointimal hyperplasia compared to Group 3 (50.06±7.50%, p <0.05). All fimasartan treated groups revealed decreased smooth muscle cell proliferation and CD68+ macrophages in carotid artery. Furthermore, inflammatory cytokines such as MMP9 and IL-6 were significantly lower in Group 4 (0.32±0.02ng/mL and 11.68±2.13pg/mL) compared to Group 3 (0.54±0.13ng/mL and 16.68±3.03pg/mL, p <0.05, respectively). In particular, TNFα and ICAM at were significantly decreased in Group 2 (5.83±2.28pg/mL and 3.76±0.84ng/mL) and Group 4 (7.32±0.95pg/mL and 5.04±1.47ng/mL) compared to Group 1 (6.64±1.34pg/mL and 4.42±0.88ng/mL) and Group 3 (9.28±1.57pg/mL and 6.31±1.60ng/mL, p <0.05, respectively). IL-10 increased significantly in Group 4 (29.20±0.52pg/mL) compared to Group 3 (26.18±1.14pg/mL, p <0.05). Conclusions: Fimasartan reduced neointimal hyperplasia with decreases in macrophages in carotid atherosclerotic plaque and with reductions in systemic inflammation in ApoE knockout mice.