Statin therapy protects against abdominal aortic aneurysms by inducing the accumulation of regulatory T cells in ApoE-/- mice.

Abstract

CD4+CD25+ 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 100μg CD25-depleting antibody PC61). After 2weeks 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 28days. Simvastatin therapy for 6weeks 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.