Grant: Travel Awards - Institute Community Support

Lysosomes are central to the metabolism of LDL-cholesterol and play an important role in both generation of foam cells in atherosclerosis and the removal of excess lipids from arterial lesions. We have previously found that smooth muscle cells (SMCs) make up >50 % of the foam cells in coronary lesions and have reduced expression of the membrane cholesterol exporter ATP-binding cassette transporter A1 (ABCA1). Expression of ABCA1 is acutely dependent on the flux of cholesterol out of lysosomes and subsequent generation of oxysterols for promotion of gene transcription by the nuclear liver X receptor (LXR). In the present studies we tested the hypothesis that SMCs have lysosomal dysfunction that contributes to foam cell formation. We find that arterial SMCs have an acute deficiency in lysosomal acid lipase, the only lysosomal cholesteryl ester hydrolase acting on LDL, expression and have defects in downstream sterol regulatory events compared to macrophages. Our results provide a novel reason for SMC foam cell formation and a potential target to reduce atherosclerosis development and promote regression therapeutically.