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Antibody‐mediated neutralization of IL11 signalling reduces ERK activation and cardiac fibrosis in a mouse model of severe pressure overload
Author(s) -
Lim WeiWen,
Corden Ben,
Ye Lei,
Viswanathan Sivakumar,
Widjaja Anissa A.,
Xie Chen,
Su Liping,
Tee Nicole G. Z.,
Schafer Sebastian,
Cook Stuart A.
Publication year - 2021
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13458
Subject(s) - pressure overload , fibrosis , medicine , cardiac fibrosis , interleukin 11 , mapk/erk pathway , signal transduction , muscle hypertrophy , immunology , microbiology and biotechnology , cancer research , pathology , cardiac hypertrophy , interleukin , biology , cytokine
Interleukin‐11 (IL11) is important for fibroblast‐to‐myofibroblast transformations. Here, we examined the signalling and phenotypic effects of inhibiting IL11 signalling using neutralizing antibodies against IL11 or its cognate receptor (IL11RA) in a mouse model of acute and severe pressure overload. C57BL/6J mice underwent ascending aortic constriction (AAC) surgery and were randomized to anti‐IL11, anti‐IL11RA, or isotype control antibodies (20 mg/kg, bi‐weekly for 2 weeks). AAC surgery induced the expression of IL11, IL11RA and extracellular matrix (ECM) genes that was associated with cardiac hypertrophy and aortic remodelling. Inhibition of IL11 signalling reduced AAC‐induced cardiac fibrosis and ECM gene expression as well as ERK1/2 phosphorylation but had no effect on cardiac hypertrophy. STAT3 was phosphorylated in the hearts of AAC‐treated mice but this was unrelated to IL11 activity, which we confirmed in mouse cardiac fibroblasts in vitro. These data highlight that blocking IL11 signalling reduces cardiac fibrosis due to severe pressure overload and suggests ERK, but not STAT3, activity as the relevant underlying signalling pathway.