Researchers discover cellular process that clears cholesterol

Ottawa, ON – Researchers at the University of Ottawa Heart Institute (UOHI) have discovered that an ancient pathway called autophagy also mobilizes and exports cholesterol from cells.

A team led by Dr Yves Marcel, director of the HDL Biology Laboratory, UOHI, has shown that autophagy, a pathway preserved during evolution, functions to engulf and digest cholesterol accumulated in artery walls. This process facilitates the removal of cholesterol and may provide an entirely new target to reverse atherosclerosis, the main cause of heart attack and stroke.

The autophagy pathway, which means self-digestion, developed early in single-cell organisms to allow the clearance of accumulated dysfunctional molecules. “The finding that autophagy also functions to digest and liberate cholesterol from cells and the fact that we know this pathway is  regulated offers hope for the development of new drugs that could activate export of cholesterol from the walls of arteries,” said Dr Marcel.

“There is an urgent need to understand how cholesterol accumulation in arteries can be reversed,” said Mireille Ouimet, who was a major contributor to the study.

Details of the research were published online recently in the journal Cell Metabolism (Cell Metab. 2011: 13(6):655-67) and illustrate how cholesterol buildup itself triggers autophagy, facilitating the release of cholesterol for transport back to the liver for elimination from the body. It is possible that some patients with coronary artery disease (CAD) have an impaired ability to clear arterial cholesterol by the autophagy pathway, according to Dr Marcel.

His work lends a greater understanding to the underlying biochemical complexities involving cholesterol. Cholesterol is important to cell structure. Problems arise when too much cholesterol is deposited inside the walls of the coronary artery – the origins of CAD.  Researchers now are investigating how this process is involved in the development of atherosclerosis, a step that could help experts in cardiovascular medicine understand and find a new way to halt the progression of heart disease.

Dr Marcel’s research career has focused on lipoproteins – the biochemical mechanism to transport cholesterol and fats through the body. In 1997, he received the McLaughlin Medal, the highest medal of honour by the Royal Society of Canada, for his contribution to medical science including research related to pathways for polyunsaturated fatty acids.