New Role for Interleukin-13 Receptor α1 in Myocardial Homeostasis and Heart Failure

Journal of the American Heart Association
Uri AmitJonathan Leor

Abstract

The immune system plays a pivotal role in myocardial homeostasis and response to injury. Interleukins-4 and -13 are anti-inflammatory type-2 cytokines, signaling via the common interleukin-13 receptor α1 chain and the type-2 interleukin-4 receptor. The role of interleukin-13 receptor α1 in the heart is unknown. We analyzed myocardial samples from human donors (n=136) and patients with end-stage heart failure (n=177). We found that the interleukin-13 receptor α1 is present in the myocardium and, together with the complementary type-2 interleukin-4 receptor chain Il4ra, is significantly downregulated in the hearts of patients with heart failure. Next, we showed that Il13ra1-deficient mice develop severe myocardial dysfunction and dyssynchrony compared to wild-type mice (left ventricular ejection fraction 29.7±9.9 versus 45.0±8.0; P=0.004, left ventricular end-diastolic diameter 4.2±0.2 versus 3.92±0.3; P=0.03). A bioinformatic analysis of mouse hearts indicated that interleukin-13 receptor α1 regulates critical pathways in the heart other than the immune system, such as extracellular matrix (normalized enrichment score=1.90; false discovery rate q=0.005) and glucose metabolism (normalized enrichment score=-2.36; false discovery r...Continue Reading

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Citations

May 22, 2017·Journal of the American Heart Association·Gustavo Ramos, Stefan Frantz
May 19, 2018·American Journal of Physiology. Heart and Circulatory Physiology·David A LiemJiaWei Han
Oct 20, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Dylan J WodsedalekCaitlin C O'Meara
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Feb 5, 2021·Cardiovascular Research·Edoardo BerteroChristoph Maack
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Aug 4, 2021·Journal of Molecular and Cellular Cardiology·Samantha J PaddockCaitlin C O'Meara

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Methods Mentioned

BETA
nuclear magnetic resonance
transgenic
biopsy
coronary artery bypass
PCR
chips
glycosylation

Software Mentioned

ImageJ
bioconductor limma package
iMAT
iMAT )
Affymetrix
GSMM
GraphPad Prism
GSEA
GraphPad
Integrative Metabolic Analysis

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