Suppression of microRNA-155 exerts an anti-inflammatory effect on CD4+ T cell-mediated inflammatory response in the pathogenesis of atherosclerosis.

In the current study, we aimed to investigate the effects of miR-155 on CD4+ T cell-mediated immune response in the pathogenesis of atherosclerosis. CD34+ hematopoietic stem cells, CD4+ T lymphocytes, endothelial cells (ECs), and vascular smooth muscle cells (VSMCs) were harvested from the same donor. Knockdown of miR-155 in the CD4+ T cells was achieved by lentiviral transfection, whereas control RNA-transfected or untransfected lymphocytes were used as controls. The transfected CD4+ T cells were activated by incubating with oxidized low-density lipoprotein-treated dendritic cells. The proliferative capacities, phenotype distribution, and cytokine secretion profiles of the activated CD4+ T cells from different groups were evaluated. The activated lymphocytes were used to treat ECs co-cultivated with VSMCs. The ability of the CD4+ T cells to induce the apoptosis of the ECs and to promote the proliferation of the VSMCs was investigated. Inhibition of miR-155 was found to significantly reduce the proliferation rate of the transfected CD4+ T cells. CD4+ T lymphocytes transfected with the miR-155 inhibitor showed increased populations of T helper type 2 and regulatory T cells, as well as more production of anti-inflammatory cytokines. MiR-155 knockdown was also shown to significantly hamper the ability to CD4+ T cells to induce EC apoptosis and to promote the growth of VSMCs. Our data suggested that inhibition of miR-155 in CD4+ T cells could slow down the formation of atherosclerotic plaques. These results lay the groundwork for future research on the therapeutic potential of miR-155 against atherosclerosis-associated cardiovascular diseases.

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