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  • Review Article
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The role of interleukin 18 in the pathogenesis of hypertension-induced vascular disease

Nature Reviews Cardiology volume 6, pages 192–199 (2009)Cite this article

Abstract

Understanding the mechanism by which chronic high blood pressure induces vascular disease is of fundamental importance for prevention of the adverse consequences of hypertension. Clinical and population studies have consistently found increased circulating levels of interleukin 18 (IL-18) in patients with hypertension. Although obesity, and possibly age, is a determinant of plasma IL-18 levels, the relationship of IL-18 to hypertension seems to be independent of these factors. Experimental evidence indicates that the expression of IL-18 and/or its receptor can be induced by catecholamines or angiotensin, two factors that are involved in the pathophysiology of hypertension. Elevated circulating IL-18 levels are associated with vascular changes in the carotid artery, including increased carotid intima–media thickness, which, in turn, is a predictor of cardiovascular events in patients with established coronary disease. IL-18, either directly or through oxidative stress pathways and matrix metalloproteins, can alter endothelial function or induce vascular smooth muscle cell migration and/or proliferation to produce the vascular changes that occur with hypertension. This Review examines the data on IL-18 and hypertensive vascular disease, and explores the potential cellular and molecular mechanisms that might connect hypertension to vascular disease.

Key Points

  • The majority of data indicate that individuals with hypertension have higher levels of circulating IL-18 than individuals with normal blood pressure

  • Although IL-18 is associated with obesity, neither age nor obesity seems to explain the relationship between IL-18 and hypertension

  • IL-18 enhances the capacity of other factors to increase reactive oxygen species production from NADPH oxidase

  • Angiotensin II enhances the expression of IL-18-induced inflammatory genes in vascular smooth muscle by increasing IL-18Rα expression

  • IL-18 increases expression of matrix metalloproteinases, which alter vascular structure

  • IL-18 might be involved in the pathways that produce hypertension-induced vascular disease

  • Catecholamines increase IL-18 production, which might account for vascular changes induced by catecholamines

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Figure 1: Simplified schematic for the effect of IL-18 on the vasculature.

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  1. Department of Medicine, University of British Columbia, Level 9, 2775 Laurel Street, Vancouver, BC V5Z 1M9, Canada rabkin@interchange.ubc.ca

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  1. SW Rabkin is a Professor of Medicine at the University of British Columbia, Vancouver, BC, Canada.,

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Rabkin, S. The role of interleukin 18 in the pathogenesis of hypertension-induced vascular disease. Nat Rev Cardiol 6, 192–199 (2009). https://doi.org/10.1038/ncpcardio1453

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