Low LAL (Lysosomal Acid Lipase) Expression by Smooth Muscle Cells Relative to Macrophages as a Mechanism for Arterial Foam Cell Formation

Objective: We previously reported smooth muscle cells (SMCs) represent ?50% of foam in human coronary and ?70% apoE (apolipoprotein E)-deficient mouse aortic atheromas exhibit reduced expression the cholesterol exporter ABCA1 (ATP-binding cassette transporter A1). A major stimulus for is flux out lysosomes, generated by hydrolysis lipoprotein cholesteryl esters LAL (lysosomal acid lipase). In this study, we investigated potential role lysosomal dysfunction might play cell formation arterial SMCs. Approach Results: Human monocyte-derived macrophages (macrophages) SMCs were treated with aggregated LDL (low-density lipoprotein) to increase intracellular postlysosomal metabolism defects. analyzed expression. Unlike macrophages, uptake failed upregulate expression, downregulate new synthesis, or significantly 27-hydroxycholesterol levels Confocal microscopy revealed retention neutral lipids within compartments SMCs, while showed most as cytosolic droplets. LIPA (lipase A) mRNA protein markedly Treatment medium containing resulted lipid accumulation increased efflux apoA-I AI). exhibited low LAL/ Lipa intimal when compared macrophages. Conclusions: These findings indicate inherently level associated capacity catabolize atherogenic lipoproteins a mechanism SMC atherosclerosis.