Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice.

Abstract

Interleukin (IL)-17A plays a role in the development of atherosclerotic plaques; however, the mechanism remains unclear. In this study, apolipoprotein E-deficient (ApoE–/–) mice were fed a high-fat diet to induce atherosclerosis, followed by the treatment with exogenous recombinant IL-17A or the neutralizing antibody to confirm the impact of IL-17A on the established atherosclerotic plaques. We found that both the stimulation of IL-17A and blockage of endogenous IL-17 via antibody did not affect the size of the established plaques. However, IL-17A significantly increased the vulnerability of plaques characterized by the accumulation of lipids and T cells with a concurrent decrease in the number of smooth muscle cells. In addition, the blockage by IL-17 neutralizing antibody attenuated plaque vulnerability. Furthermore, we found that although IL-17A did not affect the efferocytosis of macrophages to apoptotic cells, it promoted the apoptosis of macrophages in the presence of oxidized low-density lipoprotein in vitro. Also, IL-17A upregulated chemokines MCP-1 and CXCL-10 expression in the plaques. Our data indicated that IL-17A controlled both SMC and macrophage accumulation and the apoptosis within the plaque, which may further weaken the aorta wall. This study suggests that IL-17A may be a potential therapeutic target for cardiovascular diseases.