IL-18 overexpression promotes vascular inflammation and remodeling in a rat model of metabolic syndrome.
Although considerable evidence implicates the cytokine interlukin-18 (IL-18) in metabolic syndrome (MetS), the direct effect of IL-18 on vascular changes of MetS remains unknown. We investigated the chronic in vivo effect of IL-18 on development of MetS and vascular inflammation and remodeling by overexpressing IL-18 protein in fructose-fed rats (FFR), a model of MetS using intravenous administration of an adenovirus encoding rat IL-18. Increased serum IL-18 and vascular inflammatory response were found in FFR. Overexpression of IL-18 aggravated insulin resistance and enhance vascular inflammation and remodeling, which can be reflected by increased aortic expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and enhanced infiltration of macrophages and increased aortic wall thickness and wall-to-lumen ratio. Interestingly, the levels of interleukin-1 receptor-associated kinase 1 (IRAK1) and the activity of nucleus factor-kappaB (NF-kappaB) were also significantly increased. Together, these results indicated that chronic elevated IL-18 levels at a supraphsiological concentration aggravated insulin resistance, enhanced vascular inflammation and remodeling, probably by increasing the level of IRAK1 and the activity of NF-kappaB. Targeting expression of IL-18 or its specific downstream mediators may retard the progression of MetS and its complications.
Tan
Hong-Wei
HW
Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Jinan, 250012, China.
Liu
Xu
X
Bi
Xiu-Ping
XP
Xing
Shan-Shan
SS
Li
Li
L
Gong
Hui-Ping
HP
Zhong
Ming
M
Wang
Zhi-Hao
ZH
Zhang
Yun
Y
Zhang
Wei
W
D000818:Animals; D001011:Aorta / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007249:Inflammation; D007333:Insulin Resistance; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D020382:Interleukin-18 / Q000096:biosynthesis*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D020382:Interleukin-18; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; C547807:IRAK1 protein, rat; D053592:Interleukin-1 Receptor-Associated Kinases