Abstract
We assessed the role of PGC-1α (PPARγ coactivator-1 alpha) in glucose-induced proliferation, migration, and inflammatory gene expression of vascular smooth muscle cells (VSMCs). We carried out phagocytosis studies to assess the role of PGC-1α in transdifferentiation of VSMCs by flow cytometry. We found that high glucose stimulated proliferation, migration and inflammatory gene expression of VSMCs, but overexpression of PGC-1α attenuated the effects of glucose. In addition, overexpression of PGC-1α decreased mRNA and protein level of VSMCs-related genes, and induced macrophage-related gene expression, as well as phagocytosis of VSMCs. Therefore, PGC-1α inhibited glucose-induced proliferation, migration and inflammatory gene expression of VSMCs, which are key features in the pathology of atherosclerosis. More importantly, PGC-1α transdifferentiated VSMCs to a macrophage-like state. Such transdifferentiation possibly increased the portion of VSMCs-derived foam cells in the plaque and favored plaque stability.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Aorta, Thoracic / cytology
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Cell Physiological Phenomena / drug effects
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Cell Physiological Phenomena / genetics
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Cell Transdifferentiation
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Cells, Cultured
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Chemokine CCL2 / genetics
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Chemokine CCL2 / metabolism
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Gene Expression Regulation
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Glucose / pharmacology*
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Macrophages / metabolism
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Male
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Muscle, Smooth, Vascular / cytology*
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism
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Myocytes, Smooth Muscle / cytology
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Myocytes, Smooth Muscle / metabolism*
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Phagocytosis / genetics
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RNA-Binding Proteins / genetics*
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RNA-Binding Proteins / metabolism
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Rats
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Rats, Sprague-Dawley
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Transfection
Substances
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Chemokine CCL2
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Interleukin-6
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Ppargc1a protein, rat
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RNA-Binding Proteins
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Transcription Factors
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Glucose