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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Trogan, Eugene Fisher, Edward A. Rong, James X. Shapiro, Mark |
| Description | Author Affiliation: Rong JX ( Department of Medicine and The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.); |
| Abstract | Mouse aortic smooth muscle cells (SMCs) were loaded for 72 h with cholesterol by using cholesterol:methyl-beta-cyclodextrin complexes, leading to approximately 2-fold and approximately 10-fold increases in the contents of total cholesterol and cholesteryl ester, respectively. Foam-cell formation was demonstrated by accumulation of intracellular, Oil Red O-stained lipid droplets. Immunostaining showed decreased protein levels of smooth muscle alpha-actin and alpha-tropomyosin and increased levels of macrophage markers CD68 and Mac-2 antigen. Quantitative real-time RT-PCR revealed that after cholesterol loading, the expression of SMC-related genes alpha-actin, alpha-tropomyosin, myosin heavy chain, and calponin H1 decreased (to 11.5 +/- 0.5%, 29.3 +/- 1.4%, 23.8 +/- 1.4%, and 3.8 +/- 0.5% of unloaded cells, respectively; P < 0.05 for all), whereas expression of macrophage-related genes CD68, Mac-2, and ABCA1 mRNA increased (to 709 +/- 84%, 330 +/- 11%, and 207 +/- 13% of unloaded cells, respectively; P < 0.05 for all), thereby demonstrating that the protein changes were regulated at the mRNA level. Furthermore, these changes were accompanied by a gain in macrophage-like function as assessed by phagocytotic activity. Expression of vascular cell adhesion molecule 1 and monocyte chemoattractant protein 1, known responders to inflammation, were not changed. In conclusion, cholesterol loading of SMC causes phenotypic changes regulated at the mRNA level that result in a transdifferentiation to a macrophage-like state. This finding suggests that not all foam cells in lesions may have a macrophage origin, despite what is indicated by immunostaining for macrophage-related markers. Furthermore, inflammatory changes in foam cells observed in vivo may not be simple consequences of cholesterol accumulation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 23 |
| Volume Number | 100 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2003-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Aorta Metabolism Cholesterol Macrophages Myocytes, Smooth Muscle Cytology Actins Animals Antigens, CD Biosynthesis Antigens, Differentiation, Myelomonocytic Azo Compounds Pharmacology Cell Differentiation Cell Line, Tumor Cells, Cultured Cholesterol Esters Coloring Agents Cyclodextrins Dose-Response Relationship, Drug Foam Cells Galectin 3 Immunohistochemistry Mice Mice, Inbred C57BL NIH 3T3 Cells Phagocytes Phagocytosis Phenotype RNA, Messenger Reverse Transcriptase Polymerase Chain Reaction Time Factors Tropomyosin Vascular Cell Adhesion Molecule-1 Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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