Autophagy may provide an entirely new target to reverse atherosclerosis.
Autophagy, a pathway preserved during evolution, functions to engulf and digest cholesterol accumulated in artery walls. Researchers at the University of Ottawa Heart Institute (UOHI) in Canada are now finding that this process may also provide an entirely new target to reverse atherosclerosis.
“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,” Yves Marcel, PhD, director of the HDL Biology Laboratory at UOHI, said in a statement.
“There is an urgent need to understand how cholesterol accumulation in arteries can be reversed,” Mireille Ouimet, a doctoral student in Marcel’s lab and a major contributor to the study, added. The research, which was published in Cell Metabolism, illustrates 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, said Marcel.
The work lends a greater understanding to the underlying biochemical complexities involving cholesterol. Researchers now are investigating how the buildup of cholesterol in arteries 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.
Marcel's research career has focused on lipoproteins — the biochemical mechanism to transport cholesterol and fats through the body. In 1997, he received the highest medal of honor by the Royal Society of Canada for his contribution to medical science including research related to pathways for polyunsaturated fatty acids. This was the McLaughlin Medal, considered one of the country's most prestigious tributes for research excellence.
Autophagy Regulates Cholesterol Efflux from Macrophage Foam Cells Via Lysosomal Acid Lipase [Cell Metabolism]