Keeping the Engine Running

Innovative research focuses on the recovery
of damaged hearts

It’s no small irony that Dr. Ian Dixon owns a 1950 Ford half-ton that still keeps on humming. After all, his research is focused on keeping a muscular biological engine – the heart – running effectively through heart disease and major cardiac events.

Specifically, Dixon and his team are looking to slow down the progression of fibrosis which is present in most heart disease. Fibrosis is the thickening of tissue that usually takes place as a result of disease or injury, including heart attack. In case of heart attack or other cardiac issues, fibrosis impedes the heart’s ability to pump effectively. The goal of his research is to preserve and even improve cardiac function in a markedly fibroses heart.

“I was interested in what happens to people after they’ve had a large heart attack and survived, With the terrific clinical care that most of these patients currently receive, this is more and more the case,” says Dixon, Principal Investigator, Molecular Cardiology, at St. Boniface Hospital Research Centre. “If we do have a major heart attack or an MI – myocardial infarction – we can be treated, and be removed from immediate danger at the acute phase and make it through the following week or two without passing away. Then the heart compensates – becomes stronger -and it soldiers on. But the initial size of the insult or the damage to the ventricular wall is crucial to what might transpire further along.”

The size of the original infarct (a specific mass of dead tissue caused by interrupted blood flow) has a direct impact on quality of life.

“I’m interested to learn why the initial size of the infarct is so important. Why we spiral into progressive heart failure.”

Scarring in the heart

“Despite the compensation, something’s not quite right with the heart’s pumping ability and the patient’s quality of life can be impacted. If a person enjoyed long walks, or towing kids in a wagon, or doing things involving some exertion, that ability is suddenly gone,” says Dixon, who has been at St. Boniface for over 20 years. “I’m interested to learn why the initial size of the infarct is so important. Why we spiral into progressive heart failure. The sobering fact is, if the infarct is of a certain size, five years out from that infarct—let’s say most make it through acute phase—half of those people will be dead. This is sobering when one considers the rather large armament of drugs available to the clinician in treatment of the problem.”

Dixon says the challenge is that scarring in the heart is different than scarring elsewhere. A wound on the skin, for example, repairs itself and then stops. “In the heart, you have repair, which is followed by continuing or ongoing repair, which is necessarily bad.  This is attended by so-called infarct expansion – the scar actually changes shape and it in turn changes the geometry of the cardiac ventricle – a hollow muscular organ.  When this occurs it tends not to fill or eject blood properly,” he explains.

Dixon’s lab is trying to figure out why this happens – why wounds to the heart heal differently and without a “stop” signal, and what can be done about it. The focus is on two naturally-occurring proteins – Smad7 and c-Ski.  These proteins are phylogenitically ancient and are typically in place to slow wound healing.  By mimicking and augmenting the function of these proteins with newly designed agents, it might be possible to slow the fibrosis and improve how the heart heals after a heart attack.

Dixon’s specific focus on fibrosis was not his first choice. Years ago he was funded to work on an entirely different subject at the University of Toronto. Just two months into the work, a paper from a U.S. university was released on the exact same topic. “They were about a year-and-a-half ahead of us and they completely blew us out of the water. They published exactly what we were doing, so there was no wiggle room,” he recalls. He was disheartened (so to speak), but his boss at the time, Michael Sole, suggested that Dixon turn his attention to fibrosis, where very little research was happening.

The rest is history.

Dixon’s vision for Canada

At the time (around 1991), there were only a handful of labs in Canada looking at cardiac fibrosis. Today, there are over 100. Dixon and his St-Boniface colleagues, including other Principal Investigators, are seen as leaders in the field. In fact, Dixon is at the hub of MatriNET, the Matrix and Tissue Remodelling Network. MatriNET is a high-end network of 17 leading Canadian institutions focused on unravelling all of the mysteries related to fibrosis and heart health.

MatriNET is seeking to become recognized by the Networks of Centres of Excellence (NCE), a federal government designation that would open the doors to more funding and greater visibility. Dixon wrote the Letter of Intent to the NCE, one of 83 letters entertained in the summer of 2014. MatriNET made it passed the first hurdle as one of only 10 applicants invited to submit a full application.

A successful and well-funded network will allow fibrosis research to move ahead much more quickly as different kinds of specialists and experts collaborate across the country. It will also take the work from a place of basic science to applied solutions for heart patients.

“The vision that Canada can move ahead of a lot of countries in this area is going to happen, is what excites me. I think we can do it in Canada and I think Canada has a lot of advantages over other countries,” says Dixon.  “We’re small and therefore nimble – we can move quickly to implement discovery to the clinic.”

With NCE recognition and with Dixon and his St. Boniface colleagues at the hub, the research engine will continue to rev.

To learn more about Dr. Dixon’s research visit www.sbrc.ca/dixon

Dr. Ian Dixon
Principal Investigator, Molecular Cardiology,
St. Boniface Hospital Research Centre
Professor of Physiology, University of Manitoba

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