title: Pressure overload-induced cardiac remodeling and dysfunction in the absence of interleukin 6 in mice.
abstract: Congestive heart failure is associated with increased expression of pro-inflammatory cytokines, and the levels of these cytokines correlate with heart failure severity and prognosis. Chronic interleukin 6 (IL-6) stimulation leads to left ventricular (LV) hypertrophy and dysfunction, and deletion of IL-6 reduces LV hypertrophy after angiotensin II infusion. In this study, we tested the hypothesis that IL-6 deletion has favorable effects on pressure-overloaded hearts. We performed transverse aortic constriction on IL-6-deleted (IL6KO) mice and C57BL/6J mice (CON) to induce pressure overload. Pressure overload was associated with similar LV hypertrophy, dilation, and dysfunction in CON and IL6KO mice. Re-activation of the fetal gene program was also similar in pressure-overloaded CON and IL6KO mice. There were no differences between CON and IL6KO mice in LV fibrosis or expression of extracellular matrix proteins after pressure overload. In addition, no group differences in apoptosis or autophagy were seen. These data indicate that IL-6 deletion does not block LV remodeling and dysfunction induced by pressure overload. Attenuated content of IL-11 appears to be a compensatory mechanism for IL-6 deletion in pressure-overloaded hearts. We infer from these data that limiting availability of IL-6 alone is not sufficient to attenuate LV remodeling and dysfunction in failing hearts.
authors: Department of Medicine, University of California San Diego, VA San Diego Healthcare System, San Diego, CA, USA.
authors: N Chin
authors: NC
authors: Lai
authors: Mei Hua
authors: MH
authors: Gao
authors: Eric
authors: E
authors: Tang
authors: Ruoying
authors: R
authors: Tang
authors: Tracy
authors: T
authors: Guo
authors: Nancy D
authors: ND
authors: Dalton
authors: Aihua
authors: A
authors: Deng
authors: Tong
authors: T
authors: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D005260:Female; D005355:Fibrosis; D006352:Heart Ventricles / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011312:Pressure; D050796:STAT3 Transcription Factor / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse