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October 06, 2022 – For Release 12:00pm UTC

A cardiac research lab in Winnipeg is the first to discover and demonstrate the critical role of a protein called scleraxis in regulating cardiac fibrosis, a condition that stiffens the walls of the heart.

The study, published today in the European Heart Journal, shows how scleraxis is an important new factor for therapeutic targeting in a condition that currently lacks any treatment.

Fibrosis is a major clinical problem for millions of cardiac patients worldwide, contributing to arrhythmias, heart failure and death. It can develop following high blood pressure, heart attacks, diabetes and/or valve disorders, and can be monitored by MRI, but no viable therapeutics to halt or reverse the condition are currently available.

The scleraxis protein acts as a stress response pathway, playing an important role in structures rich in connective tissue like tendons and valves. Most of the existing research on how scleraxis helps and hinders our bodies, has been focused on tendons.

But the Czubryt lab has been looking at and building a case for more than a decade that scleraxis is vitally important to the heart as well and new findings show it holds the key to developing new therapeutic drugs for cardiac fibrosis.

“This work confirms that scleraxis is critical in the initiation and ongoing maintenance of cardiac fibrosis, and it should be targeted to treat this condition, improving patient quality of life and heart failure survival rates,” said Dr. Michael Czubryt, Principal Investigator, Molecular Pathophysiology, Institute of Cardiovascular Sciences, and Professor of Physiology and Pathophysiology at the University of Manitoba.

This research and the resulting paper were a major group effort involving 17 authors in total, including graduate students and fellow Principal Investigators at the Institute of Cardiovascular Sciences at St. Boniface Hospital Albrechtsen Research Centre.

Another key finding according to Czubryt, is showing that ‘fixing’ cardiac fibrosis alone is enough to improve heart function – even without halting the abnormal growth (cardiac hypertrophy) that usually accompanies disease.

“Most prior work has shown that fixing the hypertrophy did lead to improvements in fibrosis – but separating the two has been difficult,” he said.

The work involved using cutting-edge approaches including a cell-specific deletion of the scleraxis gene in mice and confirming that scleraxis levels are elevated in the hearts of human patients with dilated cardiomyopathy and high levels of collagen, which is the main component of fibrosis in the heart.

“We’re very pleased to have our work presented in a journal that commands a broad readership of cardiovascular scientists and clinicians around the globe,” says Czubryt.

The European Heart Journal is an international peer-reviewed medical journal of cardiology and cardiovascular medicine, the second highest ranking journal in this field with an impact factor of 35.8 published by Oxford University Press on behalf of the European Society of Cardiology.

Reference: Nagalingam RS, Chattopadhyaya S, Al-Hattab DS, Cheung DYC, Schwartz LY, Jana S et al. Scleraxis and fibrosis in the pressure-overloaded heart. Eur Heart J 2022. doi:10.1093/eurheartj/ehac362.

Karen Hiebert, Manager, Communications & Media Services, St. Boniface Hospital Research
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