Abstract 567: Atg16l1 Expression in Carotid Atherosclerotic Plaques Is Associated With Plaque Vulnerability
Objective: Autophagy has emerged as a cell survival mechanism critical for cellular homeostasis, which may play a protective role in atherosclerosis. ATG16L1, a protein essential for early stages of autophagy, has been implicated in the pathogenesis of inflammatory diseases such as Crohn’s disease. However, it is unknown whether ATG16L1 is involved in atherosclerosis. Our aim was to analyze ATG16L1 expression in carotid atherosclerotic plaques in relation to markers of plaque vulnerability.
Approach and results: Histological analysis of 143 endarterectomized human carotid atherosclerotic plaques revealed that ATG16L1 was expressed in areas surrounding the necrotic core and the shoulder regions. Double immunofluorescence labelling for ATG16L1 and cell type markers CD68, α-actin-smooth muscle cell, CD31 or tryptase revealed that ATG16L1 was abundantly expressed in phagocytic cells, endothelial cells, as well as mast cells in human advanced carotid plaques. ATG16L1 immunogold labelling was predominantly observed in endothelial cells and foamy smooth muscle cells of the plaques. ATG16L1 protein expression correlated with plaque content of pro-inflammatory cytokines and matrix metalloproteinases. Analysis of Atg16L1 at two distinct stages of the atherothrombotic process in a murine model of plaque rupture by incomplete ligation and cuff placement in carotid arteries of apolipoprotein-E-deficient mice, revealed a strong colocalization of Atg16L1 and smooth muscle cells only in early atherosclerotic lesions developing intimal hyperplasia.
Conclusions: Taken together, this study shows that ATG16L1 protein expression is associated with a rupture-prone and inflamed plaque phenotype, and could also contribute to the development of plaque vulnerability already at earlier stages of the atherogenic process.
Author Disclosures: J. Magné: None. P. Gustafsson: None. H. Jin: None. L. Maegdefessel: None. K. Hultenby: None. A. Wernerson: None. P. Eriksson: None. A. Franco-Cereceda: None. P. Kovanen: None. I. Gonçalves: None. E. Ehrenborg: None.
- © 2015 by American Heart Association, Inc.