BACKGROUND: Chronic inflammation plays a key role in atherogenesis, which is followed by atheromatous plaque instability. High-mobility group box 1 is released by activated macrophages as a late-phase mediator during prolonged inflammation. However, the expression of high-mobility group box 1 and its effect on the production of C-reactive protein and matrix metalloproteinases, particularly on human vascular smooth muscle cells, still remain unknown. METHODS AND RESULTS: Immunohistochemical studies revealed that high-mobility group box 1 was abundantly expressed in vascular smooth muscle cells of carotid and coronary atheromatous plaques, but not in atrophic vascular smooth muscle cells of fibrous plaques and normal medial vascular smooth muscle cells. Receptor for advanced glycation end products was also detected in vascular smooth muscle cells positive for high-mobility group box 1. Moreover, vascular smooth muscle cells positive for high-mobility group box 1 were found to express both C-reactive protein and matrix metalloproteinases (2, 3, and 9). Administration of exogenous high-mobility group box 1 to cultured vascular smooth muscle cells caused a marked elevation of C-reactive protein mRNA by reverse transcriptase-polymerase chain reaction and of C-reactive protein levels by enzyme-linked immunosorbent assay. Conversely, C-reactive protein also triggered a significant release of high-mobility group box 1 in vascular smooth muscle cell culture medium as determined by immunoblot. CONCLUSIONS: Activated vascular smooth muscle cells are the source of high-mobility group box 1 in human advanced atherosclerotic lesions. High-mobility group box 1 directly stimulates the production of both C-reactive protein and matrix metalloproteinase through receptor for advanced glycation end product. These findings provide new evidence that high-mobility group box 1 produced by activated vascular smooth muscle cells may contribute to the progression and vulnerability of human atherosclerotic lesions toward rupture.
BACKGROUND:Chronic inflammation plays a key role in atherogenesis, which is followed by atheromatous plaque instability. High-mobility group box 1 is released by activated macrophages as a late-phase mediator during prolonged inflammation. However, the expression of high-mobility group box 1 and its effect on the production of C-reactive protein and matrix metalloproteinases, particularly on human vascular smooth muscle cells, still remain unknown. METHODS AND RESULTS: Immunohistochemical studies revealed that high-mobility group box 1 was abundantly expressed in vascular smooth muscle cells of carotid and coronary atheromatous plaques, but not in atrophic vascular smooth muscle cells of fibrous plaques and normal medial vascular smooth muscle cells. Receptor for advanced glycation end products was also detected in vascular smooth muscle cells positive for high-mobility group box 1. Moreover, vascular smooth muscle cells positive for high-mobility group box 1 were found to express both C-reactive protein and matrix metalloproteinases (2, 3, and 9). Administration of exogenous high-mobility group box 1 to cultured vascular smooth muscle cells caused a marked elevation of C-reactive protein mRNA by reverse transcriptase-polymerase chain reaction and of C-reactive protein levels by enzyme-linked immunosorbent assay. Conversely, C-reactive protein also triggered a significant release of high-mobility group box 1 in vascular smooth muscle cell culture medium as determined by immunoblot. CONCLUSIONS: Activated vascular smooth muscle cells are the source of high-mobility group box 1 in human advanced atherosclerotic lesions. High-mobility group box 1 directly stimulates the production of both C-reactive protein and matrix metalloproteinase through receptor for advanced glycation end product. These findings provide new evidence that high-mobility group box 1 produced by activated vascular smooth muscle cells may contribute to the progression and vulnerability of humanatherosclerotic lesions toward rupture.
Authors: Ahmad A Mousa; Kellie J Archer; Renato Cappello; Guadalupe Estrada-Gutierrez; Christine R Isaacs; Jerome F Strauss; Scott W Walsh Journal: Reprod Sci Date: 2012-08-17 Impact factor: 3.060
Authors: Jingjing Cai; Hong Yuan; Qingde Wang; Huan Yang; Yousef Al-Abed; Zhong Hua; Jiemei Wang; Dandan Chen; Jinze Wu; Ben Lu; John P Pribis; Weihong Jiang; Kan Yang; David J Hackam; Kevin J Tracey; Timothy R Billiar; Alex F Chen Journal: Arterioscler Thromb Vasc Biol Date: 2015-10-29 Impact factor: 8.311
Authors: Ashish K Sharma; Morgan D Salmon; Guanyi Lu; Gang Su; Nicolas H Pope; Joseph R Smith; Mark L Weiss; Gilbert R Upchurch Journal: Arterioscler Thromb Vasc Biol Date: 2016-03-17 Impact factor: 8.311