Trainee's work highlighted at International meeting

Groundbreaking heart failure research is underway at the Libin Cardiovascular Institute, and it is getting noticed.

Megha Murali, a PhD candidate in the lab of Dr. Justin MacDonald, PhD, was invited to present a rapid fire talk in basic science at Heart Failure 2019, an international meeting on acute heart failure held May 25-28 in Athens, Greece, which attracted researchers and doctors from around the globe.

Her abstract was also pre-selected to be highlighted on the final day of the conference, organized by the European Society of Cardiology.

“It was exciting and really nice,” said Murali of having her work singled out. “I received lots of input and feedback and lots of people attended the session.”

Murali’s research focuses on heart failure with preserved ejection fraction (HFpEF), a condition that is mostly seen in elderly women with other conditions such as high blood pressure, obesity and diabetes. In HFpEF, the left ventricle does not relax properly, impairing its ability to fill and ultimately circulate blood.  

About 50,000 patients are diagnosed in Canada each year, and HFpEF is seen in 50 per cent of those patients, according to the Heart and Stroke Foundation’s 2016 Report on the Health of Canadians. It is growing at a rate of about one per cent each year.

Murali said despite its growing prevalence, there are few scientists researching the mechanisms of HFpEF.

Clinical evidence associates the chronic condition with inflammation of the lining of blood vessels (endothelial) and dysfunction of the minute vessels of the circulatory system. These problems in turn cause the heart to change in size and shape. 

HFpEF patients have symptoms like shortness of breath, fatigue and swelling.

For her doctoral thesis, Murali has been investigating a unique HFpEF mouse model with the smoothelin-like 1 (SMTNL1) protein genetically knocked out.

“Other (HFpEF) models don’t distinguish between males and females, nor do they separate whether it is the effect of the co-morbidities,” Murali explains.

Working with this model allowed her to study the effects of SMTNL1—without the presence of other conditions like diabetes or obesity--on the heart and vascular systems of individuals as they age.

Her findings revealed that male models without SMTNL1 developed HFpEF much earlier than their normal counterparts, suggesting that the protein may have act as a protective factor on the heart.

Further research needs to be done to determine whether females reap the same benefits from the protein, or whether their tendency to develop the disease later in life is due to the protective effect of estrogen on the heart.

The SMTNL1 protein was co-discovered in MacDonald’s lab in 2004. The lab’s continued interest in the protein stems from its novel finding that it is a regulator of blood vessel constriction and blood flow, heart function, wound repair and migration of white blood cells to sites of tissue injury and infection.

MacDonald says investigating the protein in the context of HFpEF is essential.

“The molecular pathways in the endothelium that promote HFpEF… are poorly understood, and this limits development of new therapeutic approaches for this condition,” he said.

MacDonald noted noting further investigation into the role the protein has in the cardiovascular system are merited.

“For example, how do different adaptive processes influenced by SMTNL1 integrate with comorbidities to contribute to cardiovascular health, and can it be used as a biomarker to evaluate and predict poor outcomes in HFpEF patients,” he said.

MacDonald is a member of the Libin’s Women’s Cardiovascular Research Collaborative, CV & Me. For more information about this research group, visit libin.ucalgary.ca/research/emerging-priorities/cvme.