Department of Cardiology, Cardiovascular Center, Korea University College of Medicine, Seoul, Republic of Korea.
Mol Med. 2019 Jul 15;25(1):33. doi: 10.1186/s10020-019-0095-0.
The beneficial effects of angiotensin II type 1 receptor blockers (ARBs) on atherosclerosis have been demonstrated in numerous studies. We investigated the effects of fimasartan on reducing neointimal formation and systemic inflammation after carotid artery (CA) injury in Apolipoprotein E knockout (ApoE KO) mice.
ApoE KO mice were randomly allocated to Group I (without CA injury), Group II (without CA injury + Fimasartan), Group III (CA injury), and Group IV (CA injury + Fimasartan). Fimasartan was orally administered everyday starting 3 days before iatrogenic left CA injury.
At 28 days, neointimal hyperplasia and the inflammatory cytokines including TNFα, IL-6, ICAM, and MMP-9 in the peripheral blood were significantly reduced in Groups II and IV compared to Groups I and III, respectively. All fimasartan-administered groups revealed significant increases of CD4CD25Foxp3 regulatory T (Treg) cells with increased plasma levels of IL-10 and TGFβ. In addition, increased CD8 T cells by fimasartan were correlated with reduced smooth muscle cell (SMC) proliferation in the neointima in Groups II and IV. Furthermore, the populations of Treg and CD8 T cells in total splenocytes were increased in Groups II and IV compared to Groups I and III, respectively. The enlargement of spleens due to CA injury in the Group III was attenuated by fimasartan, as shown in the Group IV. These data indicate that fimasartan significantly reduced SMC proliferation in neointima and increased Treg cells in ApoE KO CA injury mice.
This study suggests fimasartan could be an efficient strategy for reduction of atherosclerotic progression, with a decrease in immune response and systemic inflammation.
血管紧张素 II 型 1 型受体阻滞剂（ARB）对动脉粥样硬化的有益作用已在许多研究中得到证实。我们研究了在载脂蛋白 E 敲除（ApoE KO）小鼠颈动脉（CA）损伤后，非那司他对减少新生内膜形成和全身炎症的影响。
ApoE KO 小鼠随机分为四组：I 组（无 CA 损伤）、II 组（无 CA 损伤+非那司他）、III 组（CA 损伤）和 IV 组（CA 损伤+非那司他）。非那司他于 CA 损伤前 3 天开始每天口服给药。
28 天时，与 I 组和 III 组相比，II 组和 IV 组的新生内膜增生和外周血中的 TNFα、IL-6、ICAM 和 MMP-9 等炎症细胞因子明显减少。所有非那司他治疗组均显示 CD4CD25Foxp3 调节性 T（Treg）细胞显著增加，同时血浆中 IL-10 和 TGFβ水平升高。此外，非那司他增加的 CD8 T 细胞与 II 组和 IV 组新生内膜中平滑肌细胞（SMC）增殖减少有关。此外，与 I 组和 III 组相比，II 组和 IV 组的总脾细胞中 Treg 和 CD8 T 细胞的比例均增加。非那司他减轻了 CA 损伤导致的 III 组脾脏肿大，这一现象在 IV 组中更为明显。这些数据表明，非那司他可显著减少 ApoE KO CA 损伤小鼠新生内膜中 SMC 的增殖，并增加 Treg 细胞。
本研究表明，非那司他可能是减少动脉粥样硬化进展的有效策略，可降低免疫反应和全身炎症。
