BackgroundThe 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.MethodsApoE 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.ResultsAt 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 CD4+CD25+Foxp3+ 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.ConclusionsThis study suggests fimasartan could be an efficient strategy for reduction of atherosclerotic progression, with a decrease in immune response and systemic inflammation.

中文翻译：

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非马沙坦减少载脂蛋白 E 敲除小鼠颈动脉损伤后的新内膜形成和炎症

背景血管紧张素 II 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。我们研究了非马沙坦对载脂蛋白 E 敲除 (ApoE KO) 小鼠颈动脉 (CA) 损伤后新生内膜形成和全身炎症的影响。损伤 + 非马沙坦）、第 III 组（CA 损伤）和第 IV 组（CA 损伤 + 非马沙坦）。医源性左 CA 损伤前 3 天开始每天口服非马沙坦。 结果 28 天时，与组相比，第二组和第四组新生内膜增生和外周血炎性细胞因子包括 TNFα、IL-6、ICAM 和 MMP-9 显着降低分别为 I 组和 III 组。所有非马沙坦给药组均显示 CD4+CD25+Foxp3+ 调节性 T (Treg) 细胞显着增加，同时血浆 IL-10 和 TGFβ 水平增加。此外，非马沙坦增加的 CD8+ T 细胞与组 II 和 IV 中新生内膜中平滑肌细胞 (SMC) 增殖的减少相关。此外，与组 I 和 III 相比，组 II 和 IV 中总脾细胞中 Treg 和 CD8+ T 细胞的数量分别增加。如第四组所示，非马沙坦减轻了组 III 中由于 CA 损伤导致的脾脏肿大。这些数据表明非马沙坦显着降低了新内膜 SMC 增殖并增加了 ApoE KO CA 损伤小鼠的 Treg 细胞。结论本研究表明非马沙坦可能是减少动脉粥样硬化进展的有效策略，