Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein E-deficient mice

K Danzaki, Y Matsui, M Ikesue, D Ohta… - … , and vascular biology, 2012 - Am Heart Assoc
K Danzaki, Y Matsui, M Ikesue, D Ohta, K Ito, M Kanayama, D Kurotaki, J Morimoto…
Arteriosclerosis, thrombosis, and vascular biology, 2012Am Heart Assoc
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 …
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.
Am Heart Assoc