Autophagy Frees Cholesteryl Esters for Breakdown by Lysosomal Enzymes

A recently identified molecular mechanism frees cholesterol buried in macrophage foam cells and makes it available for removal from the body by the liver.

Macrophage foam cells represent a major contributor to the structure of atherosclerotic plaques. The cholesterol content of these foam cells is stored as cholesteryl esters (CEs) in vesicles known as lipid droplets (LD). Up to now, it was accepted that these cholesterol esters were metabolized by neutral CE hydrolases.

In the current study, published in the June 8, 2011, issue of the journal Cell Metabolism, investigators at the University of Ottawa Heart Institute (Canada) charted a previously unknown molecular pathway based on autophagy that resulted in the transfer of CEs from macrophage LDs to lysosomes, where lysosomal acid lipase (LAL) hydrolyzed the CEs to generate free cholesterol.

“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 form the walls of arteries,” said senior author Dr. Yves Marcel, professor of pathology and laboratory medicine at the University of Ottawa Heart Institute. “It is possible that some patients with coronary artery disease have an impaired ability to clear arterial cholesterol by the autophagy pathway.”

Related Links:
University of Ottawa Heart Institute