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Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload.


ABSTRACT: Interleukin (IL)-18 is a cardiotropic proinflammatory cytokine chronically elevated in the serum of patients with cardiac hypertrophy (LVH). The purpose of this study was to examine the role of IL-18 in pressure-overload hypertrophy using wild type (WT) and IL-18 -/- (null) mice. Adult male C57Bl/6 mice underwent transaortic constriction (TAC) for 7days or sham surgery. Heart weight/body weight ratios showed blunted hypertrophy in IL-18 null TAC mice compared to WT TAC animals. Microarray analyses indicated differential expression of hypertrophy-related genes in WT versus IL-18 nulls. Northern, Western, and EMSA analyses showed Akt and GATA4 were increased in WT but unchanged in IL-18 null mice. Our results demonstrate blunted hypertrophy with reduced expression of contractile-, hypertrophy-, and remodeling-associated genes following pressure overload in IL-18 null mice, and suggest that IL-18 plays a critical role in the hypertrophic response.

SUBMITTER: Colston JT 

PROVIDER: S-EPMC1847636 | biostudies-other | 2007 Mar

REPOSITORIES: biostudies-other

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Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload.

Colston James T JT   Boylston William H WH   Feldman Marc D MD   Jenkinson Chris P CP   de la Rosa Sam D SD   Barton Amanda A   Trevino Rodolfo J RJ   Freeman Gregory L GL   Chandrasekar Bysani B  

Biochemical and biophysical research communications 20070116 2


Interleukin (IL)-18 is a cardiotropic proinflammatory cytokine chronically elevated in the serum of patients with cardiac hypertrophy (LVH). The purpose of this study was to examine the role of IL-18 in pressure-overload hypertrophy using wild type (WT) and IL-18 -/- (null) mice. Adult male C57Bl/6 mice underwent transaortic constriction (TAC) for 7days or sham surgery. Heart weight/body weight ratios showed blunted hypertrophy in IL-18 null TAC mice compared to WT TAC animals. Microarray analys  ...[more]

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