Abstract 16720: Smooth Muscle Cells Compose a Large Percentage of Foam Cell and Macrophage-Like Cells in Human Atherosclerotic Lesions
Previous studies have shown vascular smooth muscle cells (SMCs), like macrophages, take up and store lipids to form foam cells. SMCs have also been found to express macrophage markers upon lipid loading. Although the in vivo relevance of this finding is unknown, we hypothesize that some of the foam cells thought to be monocyte-derived macrophages based on immunostaining may in fact be SMC-derived foam cells exhibiting a macrophage phenotype. The aims of the present study were to determine the contribution of monocyte-derived macrophages vs. SMCs to total lesion foam cell formation and macrophage-phenotype cells in different stages of human atherosclerosis. Lipids in formalin-fixed coronary artery tissues were preserved for staining in paraffin sections, followed by immunohistochemical staining with SM α-actin (SMC-specific), CD-45 (leukocyte common antigen), or CD-68 (macrophage) antibody and Oil Red O. Parallel studies were carried out with co-staining of SM α-actin and CD68 antibody to determine the relative content of monocyte-derived macrophages vs. CD68+ SMCs in atherosclerotic intima. We are able to distinguish SM α-actin+, CD-45+, and CD-68+ foam cells in the intima of human atherosclerotic lesions. Studies of coronary artery lesions with a high content of foam cells (stage 2 and 3, n=6 with additional samples being analyzed) show that 54.2±11.9% of foam cells are SMC-derived. Immunostaining of serial sections with SM α-actin and CD-45 antibodies revealed SM α-actin and CD-45 do not co-localize, and therefore SM α-actin can be used to distinguish SMC-derived from monocyte-derived CD68+ cells. We found that in both early and advanced lesions, some SMCs express the macrophage marker CD-68. In early stages (n=8) 18.9±3.2% of CD-68+ cells also express SM α-actin; in advanced lesions (n=13) 40.9±6.6% of CD68+ cells express SM α-actin. These studies indicate that a large percentage of foam cells and macrophage marker-expressing cells in human atherosclerotic lesions are SMC- rather than monocyte-derived. These results help to better define the main cell types over-accumulating cholesterol in atherosclerotic plaque, and to refine our understanding of atherosclerosis development and treatment.
- © 2012 by American Heart Association, Inc.