Discovery Links Gene to Protection Against Infectious Heart Disease
Vancouver, March 26, 2008 — A gene once thought to cause damage to the heart during inflammation may actually be vital for anti-virus immunity, revealed a study led by researchers at Providence Health Care's Heart + Lung Institute and the James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research at St. Paul's Hospital.
The study, published in this week's edition of Circulation, a leading journal by the American Heart Association, examined the role of the enzyme matrix metalloproteinases 9 (MMP-9) during heart inflammation resulting from coxsackievirus B3 (CVB3). This common human pathogen is the leading cause of viral myocarditis, an inflammation that can cause such severe damage to the heart that a heart transplant becomes the only treatment option.
Using special mouse models of CVB3 infection, the team of Caroline Cheung, David Marchant, Bruce McManus and others compared the effects of the virus when MMP-9 was blocked to when it was uninhibited. The results revealed a dramatic difference between the two groups of animals. When the expression of MMP-9 was blocked, the impact of the virus was much worse - the disease increased and the level of infection was much higher in the heart and pancreas than in the model which had uninhibited MMP-9. The study found that MMP-9 plays a critical role in reducing the cardiac viral load and preserving heart function.
“We have known that the levels of MMP-9 increase when the heart becomes inflamed due to virus infection. However, its exact role was unknown and many assumed that it was causative - making the damage worse,” says David Marchant, one of the lead researchers on the study. “This really alters our view on what is beneficial in potentially treating this serious disease. The results show that strategies to combat or reduce the effects of CVB3 should strongly consider MMP-9. We are hopeful that this study will help pave the way for more breakthroughs in this area.”
The full scale impact of CVB3 is difficult to determine, as there is currently no universally accepted method to diagnose infected patients, but it is estimated that Coxsackie B viruses are responsible for at least 50 per cent of the cases of infection-caused heart muscle disease wherein the viral pathogen is known.
“It is a challenge to clinically identify CVB3 and therefore difficult to verify the prevalence of the virus, but there are many studies that show the virus may be much more pervasive than we think, especially in children,” says Marchant.
The next steps for the research team will be to examine the roles of other MMPs like MMP-9 in infectious and non-infectious myocarditis.
Launched in June 2007, the Providence Heart + Lung Institute at St. Paul's Hospital merges and integrates all of Providence's heart and lung research, education and care programs under one umbrella. It is the only such institute of its kind in Canada. Its mandate is to transform cardiovascular and pulmonary research and care - transferring new care solutions from the laboratory to the clinics and communities to improve the lives of British Columbians.
The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research at St. Paul's Hospital is a UBC-affiliated research centre, focusing on the complex genetic and environmental influences that determine susceptibility to diseases of the heart, lung and vascular systems, particularly those involving inflammation or infection. Built on a 30-year history of research excellence, the iCAPTURE Centre was created in 2000 with the infusion of $21 million of technological infrastructure funding from the Canada Foundation for Innovation and its partners. In addition to its St. Paul's facility, iCAPTURE co-investigators are located at Vancouver General Hospital, UBC's Point Grey campus and the Centre for Molecular Medicine and Therapeutics.
For more information or to arrange an interview please contact Leah Lockhart at the numbers below:
Providence Health Care
Telephone: (604) 806-8882
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Providence Health Care President and CEO Dianne Doyle