RGD Reference Report - IL-18 overexpression promotes vascular inflammation and remodeling in a rat model of metabolic syndrome. - Rat Genome Database

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IL-18 overexpression promotes vascular inflammation and remodeling in a rat model of metabolic syndrome.

Authors: Tan, HW  Liu, X  Bi, XP  Xing, SS  Li, L  Gong, HP  Zhong, M  Wang, ZH  Zhang, Y  Zhang, W 
Citation: Tan HW, etal., Atherosclerosis. 2010 Feb;208(2):350-7. Epub 2009 Aug 7.
RGD ID: 4889401
Pubmed: PMID:19717152   (View Abstract at PubMed)
DOI: DOI:10.1016/j.atherosclerosis.2009.07.053   (Journal Full-text)

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.

Disease Annotations    
Metabolic Syndrome  (IEP,ISO)
vasculitis  (IDA,ISO)

Gene Ontology Annotations    

Biological Process

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Il18  (interleukin 18)

Genes (Mus musculus)
Il18  (interleukin 18)

Genes (Homo sapiens)
IL18  (interleukin 18)

Additional Information