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

Purpose of review Smooth muscle cells (SMCs) are the major cell type in human atherosclerosis-prone arteries and take up excess lipids, thereby contributing to luminal occlusion. Here we provide a focused review on pathways by which smooth muscle cells (SMCs) can become foam cells in atherosclerosis. Recent findings A synthesis of recent and older investigations provides key mechanistic insights into SMC foam cell formation. LDL and other apoB-containing lipoproteins are modified by a diverse array of oxidative, enzymatic, and nonenzymatic processes present in the arterial intima. These modifications of LDL all promote the aggregation of LDL (agLDL), a key finding from analysis of arterial lesion particles. Scavenger receptor and phagocytic capacity of SMCs can vary greatly, perhaps related to differences in SMC phenotype or in-vitro cell culture environments, and can be increased with exposure to cytokines, growth factors, and cholesterol. Macrophages promote the formation of SMC foam cells in direct or indirect co-culture models. Summary SMCs contribute significantly to the foam cell population in atherosclerosis. Further investigation and identification of key mechanisms of SMC foam cell formation will help drive new therapeutics to reduce cardiovascular disease.

A 20-year-old woman presented with abdominal pain and MRI findings of intussusception of the distal small bowel with no identifiable lead point and no visualisation of the appendix. A diagnostic laparoscopy succeeded in manually reducing the intussusception but was unable to find any candidate lead point. Intraoperatively, hyperperistalsis was observed throughout the small bowel which seemed prone to transient intussusception. Incidental appendectomy revealed an uninflamed appendix with Enterobius vermicularis (pinworm) infestation, the most common parasite present in appendectomy specimens worldwide. Although intussusception in young adults is an uncommon occurrence, the unique nature of this case is amplified by the concurrent finding of E. vermicularis infection of the appendix in an adolescent in western Canada, a phenomenon normally observed in paediatric populations with higher incidence in tropical areas. Although the mechanism of intussusception in this patient remains unclear, it is hypothesised that E. vermicularis colonisation acted as an irritant stimulating intestinal hypercontractility with resulting intussusception. Successful medical eradication of the pinworm in this individual may prevent future recurrence.