scholarly journals Histidine-rich glycoprotein inhibits high mobility group box 1-mediated signal pathway in vascular endothelial cells

Author(s):  
Shangze Gao ◽  
Hidenori Wake ◽  
Yuan Gao ◽  
Dengli Wang ◽  
Keyue Liu ◽  
...  
2019 ◽  
Author(s):  
Shangze Gao ◽  
Hidenori Wake ◽  
Masakiyo Sakaguchi ◽  
Dengli Wang ◽  
Youhei Takahashi ◽  
...  

2019 ◽  
Vol 316 (5) ◽  
pp. H1039-H1046 ◽  
Author(s):  
Yeshuo Ma ◽  
Zhen Zhang ◽  
Runtai Chen ◽  
Rui Shi ◽  
Pingyu Zeng ◽  
...  

Endothelial inflammation plays an important role in hyperhomocysteinemia (HHcy)-associated vascular diseases. High mobility group box 1 (HMGB1) is a pro-inflammatory danger molecule produced by endothelial cells. However, whether HMGB1 is involved in vascular endothelial inflammation of HHcy is poorly understood. Neuropilin-1 (NRP1) mediates inflammatory response and activates mitogen-activated protein kinases (MAPKs) pathway that has been reported to be involved in regulation of HMGB1. The aim of this study was to determine the alteration of HMGB1 in HHcy, and the role of NRP1 in regulation of endothelial HMGB1 under high homocysteine (Hcy) condition. In the present study, we first observed that the plasma level of HMGB1 was elevated in HHcy patients and an experimental rat model, and increased HMGB1 was also observed in the thoracic aorta of an HHcy rat model. HMGB1 was induced by Hcy accompanied with upregulated NRP1 in vascular endothelial cells. Overexpression of NRP1 promoted expression and secretion of HMGB1 and endothelial inflammation; knockdown of NRP1 inhibited HMGB1 and endothelial inflammation induced by Hcy, which partially regulated through p38 MAPK pathway. Furthermore, NRP1 inhibitor ATWLPPR reduced plasma HMGB1 level and expression of HMGB1 in the thoracic aorta of HHcy rats. In conclusion, our data suggested that Hcy requires NRP1 to regulate expression and secretion of HMGB1. The present study provides the evidence for inhibition of NRP1 and HMGB1 to be the novel therapeutic targets of vascular endothelial inflammation in HHcy in the future. NEW & NOTEWORTHY This study shows for the first time to our knowledge that the plasma level of high mobility group box 1 (HMGB1) is elevated in hyperhomocysteinemia (HHcy) patients, and homocysteine promotes expression and secretion of HMGB1 partially regulated by neuropilin-1 in endothelial cells, which is involved in endothelial inflammation. Most importantly, these new findings will provide a potential therapeutic strategy for vascular endothelial inflammation in HHcy.


2009 ◽  
Vol 102 (08) ◽  
pp. 352-359 ◽  
Author(s):  
Haichao Wang ◽  
Yiting Tang ◽  
Zhang Fan ◽  
Ben Lv ◽  
Xianzhong Xiao ◽  
...  

SummaryHigh-mobility group box 1 protein (HMGB1), an abundant nuclear protein, was recently established as a proinflammatory mediator of experimental sepsis.Although extracellular HMGB1 has been found in atherosclerotic plaques, its potential role in the pathogenesis of atherothrombosis remains elusive. In the present study, we determined whether HMGB1 induces tissue factor (TF) expression in vascular endothelial cells (ECs) and macrophages. Our data showed that HMGB1 stimulated ECs to express TF (but not TF pathway inhibitor) mRNA and protein in a concentration and time-dependent manner. Blockade of cell surface receptors (including TLR4, TLR2, and RAGE) with specific neutralising antibodies partially reduced HMGB1-induced TF expression. Moreover, HMGB1 increased expression of Egr-1 and nuclear translocation of NF-κB (c-Rel/p65) in ECs. Taken together, our data suggest that HMGB1 induces TF expression in vascular endothelial cells via cell surface receptors (TLR4, TLR2, and RAGE), and through activation of transcription factors (NF-κB and Egr-1).


iScience ◽  
2020 ◽  
Vol 23 (6) ◽  
pp. 101180
Author(s):  
Shangze Gao ◽  
Hidenori Wake ◽  
Masakiyo Sakaguchi ◽  
Dengli Wang ◽  
Youhei Takahashi ◽  
...  

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yuichi Nakamura ◽  
Satoshi Suzuki ◽  
Takeshi Shimizu ◽  
Makiko Miyata ◽  
Tetsuro Shishido ◽  
...  

Background: High mobility group box 1 (HMGB1) is a DNA-binding protein secreted into extracellular space from necrotic cells and acts as a cytokine. We have reported that HMGB1 attenuates cardiac damage and restores cardiac function by enhancing angiogenesis after myocardial infarction (MI). We examined the role of HMGB1 in angiogenesis from bone marrow (BM) -derived cells in the heart, using transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-TG). Methods and Results: HMGB1-TG mice and wild-type littermate (WT) mice were lethally irradiated and injected with BM cells from green fluorescent protein (GFP) mice through the tail vein. Two weeks after BM transplantation, the left anterior descending artery was ligated to create MI. In flow cytometry analysis, GFP-positive cells were identified as donor BM cells-derived endothelial progenitor cells (EPC) if they were positive for both CD34 and CD144 in granulocyte differentiation antigen-1-negative fraction. Circulating EPC mobilized from BM was increased at 1 week after MI in HMGB1-TG mice compared with WT mice (41.9% vs. 24.5%, P < 0.01). Histological examination showed the size of MI was smaller in HMGB1-TG mice than in WT mice (42.9% vs. 59.1%, P < 0.01) at 4 weeks after MI. In myocardial immunofluorescence staining, GFP and CD31 double-positive cells were BM-derived cells engrafted within myocardial tissue as vascular endothelial cells of new capillaries or arterioles. The ratio of these double positive cells to all cardiac cells was significantly higher in the HMGB1-TG mice than in the WT mice (8.3% vs. 2.9%, P < 0.01). Enzyme-linked immunosorbent assay revealed that the levels of cardiac vascular endothelial growth factor at 1 week after MI were higher in HMGB1-TG mice than in WT mice (642.1 vs. 390.7 pg/dl, P < 0.05). Conclusions: The present study demonstrated the direct in vivo evidence that HMGB1 promoted angiogenesis and reduced MI size by enhancing mobilization and differentiation of BM cells to EPC, migration to the border zone of MI, and engraftment as vascular endothelial cells of new capillaries or arterioles in the infarcted heart.


Author(s):  
Takashi Tanaka ◽  
Yasuyuki Abe ◽  
Chieh-Jen Cheng ◽  
Ryo Tanaka ◽  
Akira Naito ◽  
...  

Globally, increasing mortality from cardiovascular disease has become a problem in recent years. Vascular replacement has been used as a treatment for these diseases, but with blood vessels &lt;6 mm in diameter, existing vascular grafts made of synthetic polymers can be occluded by thrombus formation or intimal hyperplasia. Therefore, the development of new artificial vascular grafts is desirable. In this study, we developed an elastin (EL)–silk fibroin (SF) double-raschel knitted vascular graft 1.5 mm in diameter. Water-soluble EL was prepared from insoluble EL by hydrolysis with oxalic acid. Compared to SF, EL was less likely to adhere to platelets, while vascular endothelial cells were three times more likely to adhere. SF artificial blood vessels densely packed with porous EL were fabricated, and these prevented the leakage of blood from the graft during implantation, while the migration of cells after implantation was promoted. Several kinds of 13C solid-state NMR spectra were observed with the EL–SF grafts in dry and hydrated states. It was noted that the EL molecules in the graft had very high mobility in the hydrated state. The EL–SF grafts were implanted into the abdominal aorta of rats to evaluate their patency and remodeling ability. No adverse reactions, such as bleeding at the time of implantation or disconnection of the sutured ends, were observed in the implanted grafts, and all were patent at the time of extraction. In addition, vascular endothelial cells were present on the graft's luminal surface 2 weeks after implantation. Therefore, we conclude that EL–SF artificial vascular grafts may be useful where small-diameter grafts are required.


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