title: 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.
authors.affiliation: South Texas Veterans Health Care System, San Antonio, TX, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Colston
authors.forename: William H
authors.initials: WH
authors.lastname: Boylston
authors.forename: Marc D
authors.initials: MD
authors.lastname: Feldman
authors.forename: Chris P
authors.initials: CP
authors.lastname: Jenkinson
authors.forename: Sam D
authors.initials: SD
authors.lastname: de la Rosa
authors.forename: Amanda
authors.initials: A
authors.lastname: Barton
authors.forename: Rodolfo J
authors.initials: RJ
authors.lastname: Trevino
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Freeman
authors.forename: Bysani
authors.initials: B
authors.lastname: Chandrasekar
mesh_terms: D000818:Animals; D001011:Aorta / Q000601:surgery; D006332:Cardiomegaly / Q000235:genetics* / Q000503:physiopathology*; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D020382:Interleukin-18 / Q000172:deficiency* / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D020382:Interleukin-18