Association of Serum HMGB2 Levels With In-Stent Restenosis: HMGB2 Promotes Neointimal Hyperplasia in Mice With Femoral Artery Injury and Proliferation and Migration of VSMCs
| Autor: | Zhu Hui Liu, Yu Hu He, Rui Yan Zhang, Lin Lu, Xiao Xiang Yan, Xiao Qun Wang, Ke Yang, Ying Shen, Wei Feng Shen, Ling Jie Wang, Wen Qi Pan, Zheng Bin Zhu, Feng Hua Ding, Jian Zhang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pathology Swine Receptor for Advanced Glycation End Products Coronary Artery Disease 030204 cardiovascular system & hematology Coronary Angiography Muscle Smooth Vascular 0302 clinical medicine Restenosis Cell Movement Risk Factors Phosphorylation Cells Cultured Neointimal hyperplasia Mice Knockout biology Middle Aged Femoral Artery medicine.anatomical_structure Phenotype Swine Miniature Female RNA Interference Stents Cardiology and Cardiovascular Medicine Artery Signal Transduction medicine.medical_specialty Myocytes Smooth Muscle Transfection HMGB2 Coronary Restenosis 03 medical and health sciences Percutaneous Coronary Intervention Neointima medicine Animals HMGB2 Protein Humans Genetic Predisposition to Disease Femoral artery injury Aged Cell Proliferation Hyperplasia business.industry NADPH Oxidases Vascular System Injuries medicine.disease Mice Inbred C57BL Disease Models Animal 030104 developmental biology Logistic Models Case-Control Studies Multivariate Analysis biology.protein In stent restenosis business Reactive Oxygen Species Biomarkers |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 37(4) |
| ISSN: | 1524-4636 |
| Popis: | Objective— In a previous study, we established diabetic and nondiabetic minipig models with coronary artery in-stent restenosis (ISR). Mass spectrometry showed that high-mobility group box (HMGB) 2 level was higher in ISR than in non-ISR tissue from diabetic minipigs. We here investigated whether serum HMGB2 levels were related to ISR in coronary artery disease patients. The effect of HMGB2 was evaluated in mice with femoral artery wire injury and in human aortic smooth muscle cells. Approach and Results— From 2513 patients undergoing coronary artery intervention and follow-up angiography at ≈1 year, 262 patients were diagnosed with ISR, and 298 patients with no ISR were randomly included as controls. Serum HMGB2 levels were significantly higher in patients with ISR than in those without ISR and were associated with ISR severity. Multivariable logistic regression analysis showed that HMGB2 level was independently associated with ISR. In experiments, HMGB2 expression was increased in vascular tissue after injury. Perivascular HMGB2 administration promoted injury-induced neointimal hyperplasia in C57Bl/6 mice compared with in the control, whereas such pathophysiological features were attenuated in Hmgb2 –/– mice. Mechanistically, HMGB2 enhanced neointimal hyperplasia in mice and proliferation and migration in human aortic smooth muscle cells by inducing reactive oxygen species through increased p47phox phosphorylation. Knocking down p47phox, however, inhibited HMGB2-induced effects in human aortic smooth muscle cells. Finally, HMGB2-induced effects were significantly declined in receptor of advanced glycation end products knockdown or deficient cells, but not in Toll-like receptor 4 knockdown or deficient cells. Conclusions— Serum HMGB2 levels were associated with ISR in patients. HMGB2 promoted neointimal hyperplasia in mice with arterial wire injury through reactive oxygen species activation. |
| Databáze: | OpenAIRE |
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