An ancient cellular pathway called autophagy or “self-digestion” that clears accumulated dysfunctional molecules from cells, also mobilizes and exports cholesterol and may provide an entirely new target for drugs to “unfur arteries” or reverse atherosclerosis, the main cause of heart attack and stroke, according to research led by the University of Ottawa Heart Institute (UOHI) in Canada.

Lead investigator Dr Yves Marcel, Director of the HDL Biology Laboratory, UOHI, and colleagues from UOHI and Columbia University in New York, USA, found that autophagy, a process which developed in single-cell organisms and has remained preserved during evolution, engulfs and digests cholesterol that has accumulated in artery walls.

In a statement released yesterday, 8 September, Marcel told the press:

“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 the walls of arteries.”

Cholesterol is an important and necessary molecule in mammals where it produces hormones and cell membranes and is carried around the body in the blood. However, it also accumulates in the walls of arteries, causing them to “fur up” and turn into atherosclerosis, where arteries get narrower and narrower, eventually causing blockages and reduced blood flow to the heart which often results in heart attacks and strokes.

Co-researcher Mireille Ouimet, a major contributor to the work, said:

“There is an urgent need to understand how cholesterol accumulation in arteries can be reversed.”

The researchers have discovered that cholesterol accumulation itself triggers autophagy, causing cholesterol to be released and sent back to the liver, where it is broken down and removed from the body.

Marcel suggests that perhaps some people with coronary artery disease (CAD) aren’t able to clear cholesterol in their arteries by the autophagy pathway. One route for new drugs could be to re-activate this pathway.

The researchers published details of their work earlier this year in the journal Cell Metabolism.

Written by Catharine Paddock PhD