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Background  Activated T cells and dendritic cells ( DC s) are colocalized in atherosclerotic plaques in association with plaque rupture. Oxidized low‐density lipoprotein (ox LDL ) promotes immune activation and inflammation. We studied the effects of statins (atorvastatin and simvastatin) on human  DC  maturation and T‐cell activation.    Methods and Results  Human peripheral blood monocytes were differentiated to  DC s and stimulated with ox LDL . T cells were isolated from carotid endarterectomy specimens from patients undergoing carotid endarterectomy or from healthy individuals. Naïve T cells were cocultured with pretreated  DC s. The effects of statin were studied. Ox LDL  induced  DC  maturation and T‐cell activation. Ox LDL  induced atherogenic heat shock proteins ( HSP ) 60 and 90 and decreased potentially atheroprotective heat shock protein 27, effects restored by atorvastatin. T cells exposed to ox LDL ‐treated  DC s produced interferon‐γ and interleukin ( IL )‐17. Atorvastatin and simvastatin suppressed the  DC  maturation showing lower expression of  CD 80,  CD 83, and  CD 86, and limited their production of tumor necrosis factor‐α,  IL ‐1β and  IL ‐6, and increased transforming growth factor‐β and  IL ‐10 secretion. Statin‐treated  DC s inhibited Th1 and/or Th17 polarization by downregulation of transcriptional factors T‐bet and  ROR γt expression, and induced T regulatory cells with  IL ‐10 production. Ox LDL ‐induced mi RNA  let7c and phosphorylation of Akt and  ERK  were repressed by statins. Let‐7c had a pivotal role in mediating effect of ox LDL . Experiments on T cells derived from carotid atherosclerotic plaques or healthy individuals showed similar results.    Conclusions  Statins repress human DC maturation induced by ox LDL , limit T‐cell activation, and repress an atherogenic heat shock protein profile and promote induction of T regulatory cells. Micro RNA  let‐7c is integral to the effects.

journal of the american heart association

Oxidized Low‐Density Lipoprotein (Ox LDL )–Treated Dendritic Cells Promote Activation of T Cells in Human Atherosclerotic Plaque and Blood, Which Is Repressed by Statins: micro RNA  let‐7c Is Integral to the Effect