Journal
ATHEROSCLEROSIS
Volume 208, Issue 2, Pages 350-357Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2009.07.053
Keywords
Metabolic syndrome; Vascular inflammation; Remodeling; IL-18
Funding
- National Natural Science Foundation of China [30670874, 30570748, 30871038]
- National Basic Research Program of China [2009CB521904]
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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 over-expressing 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-kappa B (NF-kappa B) 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-kappa B. Targeting expression of IL-18 or its specific downstream mediators may retard the progression of MetS and its complications. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
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