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

AI Article Synopsis

  • The study investigates the role of interleukin-13 receptor α1 in the heart, finding it is downregulated in patients with end-stage heart failure.
  • Analysis of mouse models showed that deficiency of this receptor leads to severe heart dysfunction and affect important pathways like extracellular matrix and glucose metabolism.
  • These findings propose interleukin-13 receptor α1 as a potential new therapeutic target for heart disease treatment.

Article Abstract

Background: 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.

Methods And Results: 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 , is significantly downregulated in the hearts of patients with heart failure. Next, we showed that -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; =0.004, left ventricular end-diastolic diameter 4.2±0.2 versus 3.92±0.3; =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 rate q=0). Deficiency of was associated with reduced collagen deposition under normal and pressure-overload conditions.

Conclusions: The results of our studies in humans and mice indicate, for the first time, a role of interleukin-13 receptor α1 in myocardial homeostasis and heart failure and suggests a new therapeutic target to treat heart disease.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524075PMC
http://dx.doi.org/10.1161/JAHA.116.005108DOI Listing

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