Abstract 454: Repression of Map1lc3a During Atherosclerosis Progression Plays an Important Role in the Regulation of Vascular Smooth Muscle Cell Phenotype

Background: Autophagy is a cell survival mechanism, which has been implicated in atherogenesis in mouse models by studying core autophagy machinery proteins using knock-out models. MAP1LC3A and MAP1LC3B play a key role in autophagy activity and have been implicated as prognostic factors in several human cancers. However, data on the involvement of autophagy in human atherosclerotic disease and plaque vulnerability are still sparse and completely lacking with regards to the involvement of MAP1LC3. Approach and Results: Using two independent biobanks of human carotid atherosclerotic plaques, we observe that MAP1LC3A mRNA and protein levels are decreased in plaques from patients with symptomatic disease compared to asymptomatic. Notably, MAP1LC3A mRNA levels strongly correlate with vascular smooth muscle cell markers, while MAP1LC3B does not. In in vivo models, we show that MAP1LC3A mRNA is downregulated during the progression of atherosclerosis in hypercholesterolemic mice as well as upon hyperplasia induced by balloon-injury in rats. In vitro, we show that ablation of MAP1LC3A in human carotid VSMC induces a transient compensatory increase in myocardin, a master regulator of vascular smooth muscle cell phenotypic switch. Conclusions: Taken together, these results demonstrate that reduced MAP1LC3A expression is a relevant marker of vulnerable plaque phenotype, suggesting an impact on vascular smooth muscle cell biology in the context of atherogenesis.