Effect of PGC-1α on Proliferation, Migration, and Transdifferentiation of Rat Vascular Smooth Muscle Cells Induced by High Glucose

• Published in: Journal of biomedicine & biotechnology 2012-01, Vol.2012 (2012), p.1-8
• Main Authors: Qi, Xiaoqiang, Zhang, Yujing, Li, Jing, Hou, Dongxia, Xiang, Yang
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Aorta, Thoracic - cytology; Cell Physiological Phenomena - drug effects; Cell Physiological Phenomena - genetics; Cell Transdifferentiation; Cells, Cultured; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Gene Expression Regulation; Glucose - pharmacology; Interleukin-6 - genetics; Interleukin-6 - metabolism; Macrophages - metabolism; Male; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Myocytes, Smooth Muscle - cytology; Myocytes, Smooth Muscle - metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Phagocytosis - genetics; Rats; Rats, Sprague-Dawley; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Transfection
• ISSN: 1110-7243; 1110-7251
• DOI: 10.1155/2012/756426

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.