The Key Laboratory of Cardiovascular Remodeling and Function Research, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.
J Mol Med (Berl). 2022 Jul;100(7):1057-1070. doi: 10.1007/s00109-022-02213-3. Epub 2022 Jun 15.
CD4CD25 regulatory T cells (Tregs) have been shown to protect against abdominal aortic aneurysm (AAA) progression. Statins have immunomodulatory properties, and their effect on AAA partly depends on immune-related mechanisms. In this study, we aimed to explore whether there is an association between statins and Tregs in AAA progression. Sixty ApoE mice were randomly divided into four groups (n = 15 per group): A, saline group; B, control group; C, simvastatin group (intragastric administration of simvastatin); and D, PC61 group (simvastatin combined with an intraperitoneal injection of 100 μg CD25-depleting antibody PC61). After 2 weeks of simvastatin treatment, the mice received a continuous subcutaneous infusion of angiotensin II (Ang II; B, C, and D groups) or saline (A group) for 28 days. Simvastatin therapy for 6 weeks significantly decreased the incidence and severity of AAA and inhibited the apoptosis of smooth muscle cells and generation of reactive oxygen species, which was partly abolished after the injection of PC61 antibody. Importantly, simvastatin increased the number of Tregs and the levels of Treg-associated cytokines (TGF-β and IL-10) and decreased the level of IL-17 both in aortic tissues and serum. Interestingly, simvastatin attenuated Ang II-induced gut microbial dysbiosis, which might be associated with the accumulation of Tregs. In conclusion, simvastatin therapy prevented the development of AAA induced by Ang II in ApoE mice, which might be partly due to the induction of Treg accumulation. In addition, simvastatin regulated gut microbial dysbiosis, which might also be associated with Treg generation.
CD4CD25 调节性 T 细胞（Tregs）已被证明可防止腹主动脉瘤（AAA）的进展。他汀类药物具有免疫调节特性，其对 AAA 的作用部分取决于免疫相关机制。在这项研究中，我们旨在探讨他汀类药物与 AAA 进展中的 Tregs 是否存在关联。60 只 ApoE 小鼠被随机分为四组（每组 n = 15）：A 组，生理盐水组；B 组，对照组；C 组，辛伐他汀组（辛伐他汀灌胃）；D 组，PC61 组（辛伐他汀联合腹腔注射 100μg CD25 耗竭抗体 PC61）。辛伐他汀治疗 2 周后，小鼠接受持续皮下输注血管紧张素 II（Ang II；B、C 和 D 组）或生理盐水（A 组）28 天。6 周的辛伐他汀治疗显著降低了 AAA 的发生率和严重程度，并抑制了平滑肌细胞的凋亡和活性氧的产生，而在注射 PC61 抗体后，这种抑制作用部分被消除。重要的是，辛伐他汀增加了 Tregs 的数量以及 Treg 相关细胞因子（TGF-β 和 IL-10）的水平，并降低了主动脉组织和血清中 IL-17 的水平。有趣的是，辛伐他汀减轻了 Ang II 诱导的肠道微生物失调，这可能与 Tregs 的积累有关。总之，辛伐他汀治疗可预防 Ang II 诱导的 ApoE 小鼠 AAA 的发生，这可能部分归因于 Treg 的积累。此外，辛伐他汀调节肠道微生物失调，这也可能与 Treg 的产生有关。
