Losartan Attenuates Atherosclerosis in Uremic Mice by Regulating Treg/Th17 Balance via Mediating PTEN/PI3K/Akt Pathway

Abstract

<b><i>Introduction:</i></b> Uremia could accelerate atherosclerosis (AS) formation involving Treg/Th17 imbalance. Losartan regulates the imbalance between regulatory T cells (Treg cells) and T helper 17 cells (Th17 cells). However, their interactions in uremia accelerated AS (UAAS) remained poorly understood. <b><i>Methods:</i></b> UAAS mice model was established, and after losartan and VO-OHpic (VO, phosphatase and tensin homolog [PTEN] inhibitor) injection, biological indexes, and inflammatory cytokines (transforming growth factor-β1, TGF-β1; interleukin-10 [IL-10]; IL-17 and IL-6) levels were determined using enzyme-linked immunosorbent assay. Pathological changes on aorta were observed using hematoxylin-eosin staining. Percentages of Treg cells (CD4⁺CD25⁺Foxp3⁺) and Th17 cells (CD4⁺IL-17⁺) in total CD4⁺ T cells were determined using flow cytometry. PTEN expressions were measured using Western blot, quantitative real-time polymerase chain reaction, and immunohistochemistry staining as needed. <b><i>Results:</i></b> After UAAS mice model construction, biological indexes (urea, cholesterol, and triglycerides) levels were increased, and aortic atherosclerotic plaque was formed. In UAAS mice, in total CD4⁺ T cells, Treg cells percentage was decreased yet Th17 cells percentage was increased, and TGF-β1 and IL-10 levels were downregulated yet IL-17 and IL-6 levels were upregulated. An opposite effect was found after losartan treatment. PTEN was downregulated in UAAS mice, and suppressing PTEN reversed the alleviating effects of losartan in UAAS mice. <b><i>Conclusion:</i></b> Losartan attenuated UAAS in mice by regulating Treg/Th17 cells balance via mediating PTEN/PI3K/Akt pathway, providing possible therapeutic method for UAAS in clinical practice.