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Study could lead to new treatments for pulmonary hypertension and right heart failure


February 28, 2023

“If we find something similar in humans, it could open the door to the development of new, personalized treatments for this devastating disease,” - Dr. Duncan StewartThe human heart has a remarkable ability to adapt and compensate in the face of injury and disease, but unfortunately this isn’t universal.

Some people with pulmonary arterial hypertension (PAH) have a five-year survival rate of more than 90% because the right side of their heart effectively remodels and strengthens itself to adapt to the high blood pressure in the lungs. But others with PAH can’t adapt and their five-year survival rate is less than 30%.

A discovery by Dr. Jason Zelt, MD/PhD student in Dr. Duncan Stewart’s lab could explain this difference and lead to new treatments. The study, published in Hypertension, builds on the Stewart lab’s previous research showing that one common type of lab rat can adapt to PAH while another cannot.

Their new research shows that the non-adapting rats (Fischer strain) had more than a 10-fold reduction in the level of a protein called adenylate kinase 1 (AK1). Genome-wide sequencing revealed a genetic variant that may be responsible.

“If we find something similar in humans, it could open the door to the development of new, personalized treatments for this devastating disease,” said Dr. Stewart, senior scientist and Executive Vice-President of Research at The Ottawa Hospital and professor at the University of Ottawa.

Dr. Jason ZeltDr. Jason Zelt, MD/PhD student in Dr. Duncan Stewart’s labAuthors: Zelt JGE, Cadete V, Deng Y, Godoy R, Cuillerier A, Rowe K, Abdul-Ghani M, Megeney L, Burelle Y, Giulivi A, Stewart AFR, Provencher S, Breuils-Bonnet S, Bonnet S, deKemp R, Beanlands R, Mielniczuk LM, Stewart DJ.

Core resources: StemCore, Proteomics, Metabolomics

Funding: Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Vanier Canada Graduate Scholarship, Vered Chair in Cardiology, Heart Stroke Foundation, University of Ottawa. All research at The Ottawa Hospital is enabled by generous donors to The Ottawa Hospital Foundation.

The Ottawa Hospital is a leading academic health, research and learning hospital proudly affiliated with the University of Ottawa and supported by The Ottawa Hospital Foundation.