ABSTRACT
[Figure: see text].
Subject(s)
Atherosclerosis/enzymology , Cholesterol/metabolism , Foam Cells/enzymology , Muscle, Smooth, Vascular/enzymology , Myocytes, Smooth Muscle/enzymology , Sterol Esterase/metabolism , Animals , Aorta/enzymology , Aorta/pathology , Atherosclerosis/genetics , Atherosclerosis/pathology , Disease Models, Animal , Foam Cells/pathology , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout, ApoE , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/pathology , RAW 264.7 CellsABSTRACT
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.
