Interleukin-17A Deficiency Accelerates Unstable Atherosclerotic Plaque Formation in Apolipoprotein E-Deficient Mice
Objective—Interleukin(IL)-17A, an inflammatory cytokine, has been implicated in atherosclerosis, in which inflammatory cells within atherosclerotic plaques express IL-17A. However, its role in the development of atheroscelrosis remains to be controversial.
Methods and Results—To directly examine the role of IL-17A in atherosclerosis, we generated apolipoprotein E (ApoE)/IL-17A double-deficient (ApoE−/−IL-17A−/−) mice. Mice were fed with high-fat diet (HFD) for either 8 or 16 weeks, both starting at ages of 6 to 8 weeks. We found that splenic CD4+ T-cells produced high amounts of IL-17A in ApoE−/− mice after HFD feeding for 8 weeks. Atherosclerosis was significantly accelerated in HFD-fed ApoE−/−IL-17A−/− mice compared with ApoE−/− mice. Splenic CD4+ T-cells of ApoE−/−IL-17A−/− mice after HFD feeding for 8 weeks, but not for 16 weeks, exhibited increased interferon gamma and decreased IL-5 production. Importantly, formation of vulnerable plaque as evidenced by reduced numbers of vascular smooth muscle cells and reduced type I collagen deposition in the plaque was detected in ApoE−/−IL-17A−/− mice after HFD feeding for 8 weeks.
Conclusion—These results suggest that IL-17A regulates the early phase of atherosclerosis development after HFD feeding and plaque stability, at least partly if not all by modulating interferon gamma and IL-5 production from CD4+ T-cells.
- Received April 25, 2011.
- Accepted November 9, 2011.
- © 2011 American Heart Association, Inc.