Interleukin-17A Deficiency Accelerates Unstable Atherosclerotic Plaque Formation in Apolipoprotein E-Deficient Mice

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 32; no. 2; pp. 273 - 280
• Main Authors: Danzaki, Keiko, Matsui, Yutaka, Ikesue, Masahiro, Ohta, Daichi, Ito, Koyu, Kanayama, Masashi, Kurotaki, Daisuke, Morimoto, Junko, Iwakura, Yoichiro, Yagita, Hideo, Tsutsui, Hiroyuki, Uede, Toshimitsu
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.02.2012; Lippincott Williams & Wilkins
• Subjects: Animals; Aorta - metabolism; Aorta - pathology; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Atherosclerosis (general aspects, experimental research); Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - physiopathology; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Coronary heart disease; Dietary Fats - adverse effects; Disease Models, Animal; Disease Progression; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Heart; Immunoglobulin G - metabolism; Interferon-gamma - metabolism; Interleukin-17 - deficiency; Interleukin-17 - genetics; Interleukin-17 - therapeutic use; Interleukin-5 - metabolism; Lipid Metabolism - physiology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Plaque, Atherosclerotic - metabolism; Plaque, Atherosclerotic - physiopathology; Plaque, Atherosclerotic - prevention & control; interferon gamma; Deficiency; Interleukin; Cytokine; Rodentia; CD4 positive T cells; Cardiovascular disease; high fat diet; Vascular disease; Vertebrata; Mammalia; Mouse; Apolipoprotein E; Atherosclerotic plaque; Animal; Atherosclerosis; T-Lymphocyte; interleukin-17A; Gamma interferon
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/ATVBAHA.111.229997

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 (ApoEIL-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 ApoEIL-17A mice compared with ApoE mice. Splenic CD4 T-cells of ApoEIL-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 ApoEIL-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.