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High Mobility Group Box 1 (HMGB1) Mediates High-Glucose-Induced Calcification in Vascular Smooth Muscle Cells of Saphenous Veins.
- Source :
-
Inflammation . Dec2013, Vol. 36 Issue 6, p1592-1604. 13p. - Publication Year :
- 2013
-
Abstract
- Diabetes accelerates saphenous vein grafts calcification after years of coronary artery bypass grafting (CABG) surgery. Vascular smooth muscle cells (VSMC) undergoing a phenotypic switch to osteoblast-like cells play a key role in this process. The receptor for advanced glycation and products (RAGE) and toll-like receptors (TLRs) are all involved in various cardiovascular calcification processes. Therefore, the role of their common ligand, high mobility group box 1 (HMGB1), in high-glucose-induced calcification in VSMC of saphenous vein was investigated. In this study, VSMC were cultured from saphenous vein of patients arranged for CABG. We first demonstrated high-glucose-induced HMGB1 translocation from nucleus to cytosol, and this translocation was induced through a NADPH oxidase and PKC-dependent pathway. We next found high glucose also increased TLR2, TLR4, and RAGE expression. Then, we revealed downregulating HMGB1 expression abolished high-glucose-induced calcification accompanied by NFκB inactivation and low expression of bone morphogenetic protein-2 (BMP-2). We further demonstrated NFκB activation was necessary in high-glucose-induced BMP-2 expression and calcification. Finally, by using a chromatin immunoprecipitation assay, we demonstrated NFκB transcriptional regulation of BMP-2 promoter was induced by NFκB binding to its κB element on the BMP-2 promoter. Our findings thus suggest HMGB1 plays an important role in mediating the calcification process induced by high glucose through NFκB activation and BMP-2 expression in VSMC of saphenous vein. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03603997
- Volume :
- 36
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 91842231
- Full Text :
- https://doi.org/10.1007/s10753-013-9704-1