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New Role for Interleukin-13 Receptor ?1 in Myocardial Homeostasis and Heart Failure.

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 ?1 chain and the type-2 interleukin-4 receptor. The role of interleukin-13 receptor ?1 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 ?1 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 ?1 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 rate q=0). Deficiency of Il13ra1 was associated with reduced collagen deposition under normal and pressure-overload conditions.The results of our studies in humans and mice indicate, for the first time, a role of interleukin-13 receptor ?1 in myocardial homeostasis and heart failure and suggests a new therapeutic target to treat heart disease.

SUBMITTER: Amit U

PROVIDER: S-EPMC5524075 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Amit Uri U Kain David D Wagner Allon A Sahu Avinash A Nevo-Caspi Yael Y Gonen Nir N Molotski Natali N Konfino Tal T Landa Natalie N Naftali-Shani Nili N Blum Galia G Merquiol Emmanuelle E Karo-Atar Danielle D Kanfi Yariv Y Paret Gidi G Munitz Ariel A Cohen Haim Y HY Ruppin Eytan E Hannenhalli Sridhar S Leor Jonathan J

Journal of the American Heart Association 20170520 5

<h4>Background</h4>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.<h4>Methods and results</h4>We analyzed myocardial samples from human donors (n=136) and patients with end-stage heart failure (n=177). We found that the interleukin-13 ...[more]

PMID: 28528324

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Dataset Information

New Role for Interleukin-13 Receptor ?1 in Myocardial Homeostasis and Heart Failure.

Publications

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

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