Statins Induce the Accumulation of Regulatory T Cells in Atherosclerotic Plaque

Abstract

+ regulatory T cells (Tregs) mediate immune suppression and prevent autoimmune disorders. Recently, Tregs were found to present in atherosclerotic lesions and play an important role in the progression of atherosclerosis. Statins have immunomodulatory properties, and the effect of statins on atherosclerosis depends in part on their immunomodulatory mechanisms. We sought to determine whether statins exhibit an effect on Tregs in atherosclerotic plaques and in peripheral circulation of patients with acute coronary syndrome (ACS). In an in vivo experiment, we induced atherosclerotic plaques in apolipoprotein E-deficient (ApoE

Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis

“…As expected, inhibition of lipolysis by a known inhibitor, acipimox (Guo et al., 2009), and inhibition of cholesterol synthesis by simvastatin (Meng et al., 2012) significantly attenuated cold-induced hyperlipidemia, atherosclerotic plaque growth, and instability (Figures 3G, 3H, and S3A). Consistent with this finding, blood levels of LDL cholesterol, but not HDL cholesterol, were significantly reduced by both drugs.…”

Immune Imbalances in Non-Alcoholic Fatty Liver Disease: From General Biomarkers and Neutrophils to Interleukin-17 Axis Activation and New Therapeutic Targets

“…Recent studies have increasingly highlighted the immunomodulatory role of statins (132–134); and shown in some diseases (other than NAFLD), its potential to interfere in the IL-17 axis, both by inhibiting the differentiation of Th17 cells, decreasing the production of IL-17 (62, 133, 135, 136), and inducing upregulation and recruitment of Treg (133, 137–139), shifting thus T cells response to Treg dominance (134, 140), which has an anti-inflammatory role and is a coordinator of immunologic tolerance (98, 99). This effect was also evident in atherosclerosis where the administration of statins was associated with the accumulation of T regulatory cells in atherosclerotic plaque (141, 142). Among the mechanisms underlying this effect on Treg induction is by modulating the TGF-β1 signal transduction (139).…”

The Influence of Atorvastatin and Rosuvastatin in Atherosclerosis on the Parameters of Cellular Immunity and in Vitro Leucocyte Activation

“…Оказалось, что во всех случаях первый был более эффективен (IC50 ~0,013 против 5,6 мкМ, соответственно). Добавление в культуру мононуклеарных клеток крови человека аторвастатина, но не мевастатина и правастатина, способствовало увеличению отно-сительного количества CD4+Foxp3+ Тreg [6]; инку-бация мононуклеарных клеток крови пациентов с острым коронарным синдромом в присутствии симвастатина также приводила к увеличению содер-жания в культуре Тreg и усилению их иммуносупрес-сорных свойств [12].…”