Signalling protein found to drive heart scarring and organ failure

A part of the immune system once thought to prevent organ damage is actually a leading cause of scarring and heart failure, a study has found.

Researchers at Imperial College London discovered that a protein called interleukin 11 (IL-11) plays a key role in the scarring process, which in turn causes heart, kidney and liver failure.

The research, published in the journal Nature, also found that inhibiting IL-11 could prevent the build-up of excess connective tissue in the hearts and kidneys of mice, a process called fibrosis.

The researchers are hopeful that the findings could pave the way for new treatments to prevent fibrosis and organ failure.

After a heart attack many patients may go on to develop heart failure, due to scars forming in the damaged heart muscle. Scarring is a natural response to tissue injury, but too much of it can stop organs from working effectively, and even leading to the organ starting to fail.

Heart-breaking changes

In the heart, the excess of scar tissue stops the heart muscle from contracting properly and reduces the organ’s ability to pump blood around the body.

In the latest study, researchers used cell models and mice to show that IL-11 is crucial to the scarring process, providing another target for treatment.

“We’ve discovered that IL-11 is a critical fibrotic factor and required for fibrosis to occur,” said Professor Stuart Cook, head of the Cardiovascular Genetics and Genomics group at the National Heart and Lung Institute, and one of the study’s authors.

“Scientists and pharmaceutical companies have been searching for such a factor for decades and this is a very exciting breakthrough,” he added.

Blocking the signal

Interleukins are proteins involved in relaying signals between cells. They are known to help regulate cell growth, differentiation, and movement and are particularly important in immune responses, inflammation, and fibrosis. 

By developing drugs capable of blocking IL-11 the team hopes to be able to reduce the damage caused by a heart attack and prevent the onset of devastating heart failure.

Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation – which funded Professor Cook, said: "More than half a million people are living with debilitating heart failure across the UK, for which there are limited treatments and no cure.

"Professor Cook’s team has rapidly reached the point where drug optimisation can be carried out and a clinical trial performed. This treatment could become the first to be able to successfully reduce the severe consequences of scarring in the heart.”

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‘IL11 is a crucial determinant of cardiovascular fibrosis’ by Schafer, S. et al, is published as a Letter in Nature.

This article is based on materials provided by the British Heart Foundation. 

See the press release of this article