Investigating arteries from the cell to the clinic

558

Obesity, smoking, poor diet, high blood pressure and diabetes. While we all know the major risk factors for heart disease, less well-known is the fact that clogged arteries are not simply a “plumbing” problem. Research now shows that arterial disease results to a large extent, from the body’s own protective immune reactions run amok.

Inflammation is, of course, the body’s natural response to a wound or infection. Redness and swelling occur as extra blood brings circulating immune cells to do battle with any invading organisms. Chemical signals then damp down that immune response once an infection is cleared or the wound heals. This normal immune rebalancing, however, is somehow derailed in the millions of North Americans who die of complications of atherosclerosis, the process by which fatty deposits build up in the inner lining of an artery and form yellowish plaques.

“Blood vessels have got to be the world’s perfect healers as they are getting continuously bombarded by blood pressure,” explains clinician-scientist Dr. Geoffrey Pickering, a cardiologist whose research as co-director of the Vascular Biology Group at Robarts Research Institute explores the genetic and cellular mechanisms involved in the fibrous cap that forms over arterial plaque and keeps it stable. “If we can understand the genetic factors and cellular mechanisms behind how these deposits grow, and why some become unstable but others don’t, we may be able to improve the odds for millions of people at risk of heart attack and stroke.”

Since Robarts’ inception, atherosclerosis and stroke have been key areas of research at the Institute. From the clinic to the cellular level, the Robarts approach involves novel collaborations among scientists across a range of disciplines. Scientist Dr. David Spence, for example, director for the last 25 years of Canada’s first Stroke Prevention Clinic and Atherosclerosis Research Centre in London, Ont., estimates he has seen more than 16,000 patients, many of whom have been involved in innovative projects with imaging and genomics experts that aim to better manage risk factors for stroke and discover new therapeutic targets.

For endocrinologist and scientist Dr. Robert Hegele, improving the odds for his patients starts with decoding the genetic aberrations that have left many of them vulnerable to premature heart disease and diabetes. He has discovered the molecular genetic basis of seven human diseases and his lab has identified more than 80 human mutations contributing to dyslipidemia, diabetes and atherosclerosis. Those genetic profiles then shed light on novel pathways involved in the initiation and progression of atherosclerosis and offer new insights into treatment, particularly through collaborative projects with cell biologists and imaging scientists at Robarts’ Imaging Research Laboratories.

“What all researchers are seeking is a common understanding of diseases like atherosclerosis and diabetes – from gene to cell to whole body to population – in the hope that we can find points along that continuum where appropriate interventions may be able to prevent, treat or cure these very common and deadly diseases,” Dr. Hegele says.

An interventional cardiologist, Dr. Alexandra Lucas is another Robarts clinician-scientist with an interest in improving outcomes for her patients at risk of recurring heart attacks. Using techniques in optical imaging, she investigates how unstable plaques develop as well as studying the anti-inflammatory effect of unique viral proteins and the role of vascular serpins, a super-family of proteins common in plasma, which is the accelerated growth of plaques.

Scientist Dr. Murray Huff, among his research interests, explores molecular mechanisms involved in lipoprotein metabolism and the formation of foam cells that make up the “fatty core” of an atherosclerotic plaque. “If we can determine how the lipoproteins are assembled and secreted and the role they play in plaque formation, we can define new therapeutic targets whereby production can be diminished, reducing the risk of premature cardiovascular disease.”

Linda Quattrin is director of communications at Robarts Research Institute and editor of Robarts Research magazine. She can be reached at lquattrin@robarts.ca