Interleukin-18 knockout mice display maladaptive cardiac hypertrophy in response to pressure overload.
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.
Colston
James T
JT
South Texas Veterans Health Care System, San Antonio, TX, USA.
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
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
D020382:Interleukin-18