February 24, 2014 – Providence Health Care Research Institute
BY PAMELA FAYERMAN, VANCOUVER SUN
Thirty two B.C. heart transplant patients, ranging in age from 24 to 78, gave St. Paul’s Hospital scientists permission to dissect their extracted, diseased hearts, which enabled them to make some important discoveries about how and where fatty deposits (cholesterol) accumulate in heart vessel walls.
The research, conducted over the past three years and funded by a $300,000 grant from the Heart and Stroke Foundation of BC/Yukon, alters conventional wisdom about where cholesterol accumulates in plaque. Coronary heart disease develops when the lining inside coronary arteries (the ones that supply blood to the heart) develop atherosclerosis, a condition in which the lining gets narrow, stiff and swollen as it becomes clogged up with calcium deposits, fatty deposits (cholesterol) and abnormal inflammatory cells — all of which are referred to as plaques.
Atherosclerosis is the main cause of heart attacks and strokes.
Dr. Gordon Francis, director of the Healthy Heart Prevention Clinic at St. Paul’s and an endocrinologist who treats patients with lipid disorders, is the lead author of the new study published in the journal Circulation.
The standard thinking was that cholesterol mostly accumulates in cells called macrophages, large white blood cells that fight infections and foreign particles, Francis said in an interview. But the new study points the finger at smooth muscle cells just as much, or more so.
“This is a leap in our understanding … and it potentially shows new targets to go after. It allows us to look at (cardiovascular) disease from a new perspective to develop new treatments and preventive measures,” he said.
The study is the first of its kind in humans to show that when it comes to the way cholesterol is metabolized, smooth muscle cells are just as important, or possibly more so, than macrophages. The study demonstrates the relative inability of smooth muscle cells to clear excess amounts of cholesterol, compared to macrophages. Whether cholesterol-lowering medication and other interventions are effective at helping smooth muscle cells clear out coronary arteries is a question that should now be explored, Francis agreed.
He said Vancouver researchers are now poised to make further contributions to the field of cardiovascular disease research, using an ever-growing collection of preserved organs and tissues in the Cardiovascular Registry in the Centre for Heart Lung Innovation, a Providence Health Care agency.
The registry is rather unique in the world since most medical research centres use mouse or animal models, because human tissue banks are so complex to set up and operate, Francis said.
Collecting organs and tissues is a 24-7, on-call process.
“Researchers get alerted by surgeons at all times of the day and night about donor tissues we can potentially collect and preserve for research purposes,” he said, adding that patient consent is an important part of the process.
Most transplant patients who are approached do consent to donating their removed (explanted) hearts, he said.
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