Role of Cytochrome P4501B1 in Benzo[a]pyrene Bioactivation to DNA-Binding Metabolites in Mouse Vascular Smooth Muscle Cells: Evidence from 32P-Postlabeling for Formation of 3-Hydroxybenzo[a]pyrene and Benzo[a]pyrene-3,6-quinone as Major Proximate Genotoxic Intermediates

2003 ◽  
Vol 305 (1) ◽  
pp. 394-401 ◽  
Author(s):  
Bhagavatula Moorthy ◽  
Kimberly P. Miller ◽  
Weiwu Jiang ◽  
E. Spencer Williams ◽  
Sudha R. Kondraganti ◽  
...  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoqiang Qi ◽  
Yujing Zhang ◽  
Jing Li ◽  
Dongxia Hou ◽  
Yang Xiang

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.


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