Isoliquiritigenin Inhibits Atherosclerosis by Blocking TRPC5 Channel Expression

Isoliquiritigenin (ISL) is a flavonoid isolated mainly from the licorice plant, a traditional Chinese herb. ISL has shown anticancer, anti-inflammatory, antioxidant, and antidiabetic activities. However, the pharmaceutical effects of ISL on atherosclerosis are seldom explored. In this study, we used apolipoprotein E (ApoE) knockout mouse model and angiotensin II- (Ang II-) stimulated vascular smooth muscle cells (VSMCs) to elucidate the pharmacological mechanism of ISL to inhibit atherosclerosis. We found that in ApoE−/− mice ISL could attenuate atherosclerotic lesion, reduce serum lipid levels, and inhibit TRPC5 expression. In vitro, ISL inhibited Ang II-stimulated proliferation of VSMCs and suppressed Ang II-induced TRPC5 and PCNA expressions in a dose-dependent fashion. In conclusion, our findings provide novel insight into the pharmacological effects of ISL on atherosclerosis and suggest that ISL is beneficial for cardiovascular protection.

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

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.