INFLAMMATION
·
2019
·Vol. 42
·期 6
·1951-1956
·
IF 2.939
Guo Jing,Yang Zu-Cheng,Liu Yi
The endothelial glycocalyx has been proved to be a polysaccharide protein complex covering the surface of vascular endothelial cells, playing an important role in vascular permeability, blood flow shear stress induction, and prevention of endothelial cell adhesion. The pathogenesis of PAH includes pulmonary arterial endothelial cell dysfunction and pulmonary arterial smooth muscle cell (PASMCs) proliferation. Based on the physicochemical properties of endothelial glycocalyx involving pathogenesis of pulmonary hypertension. We hypothesized that the endothelial glycocalyx is involved in the development of pulmonary hypertension; pulmonary hypertension can be regulated by protecting the integrity of glycocalyx. Expression of glycocalyx markers including heparin sulfate proteoglycan (HSPG), hyaluronan (HA), and syndecan-1 (SDC-1) was detected in monocrotaline (MCT)-induced PAH in rats and these components were detected when the PAH rats were treated with heparin that protected the role of glycocalyx. Results showed that plasma levels of HSPG, HA, and SDC-1 were increased in MCT group when compared with control group. However, rats in treatment group showed reduced levels of HSPG, HA, and SDC-1. Expression of HSPG, HA, and SDC-1 in pulmonary arteries was also reduced in MCT group when compared with those in the control group. By contrast, expression of HSPG, HA, and SDC-1 in pulmonary arteries increased in treatment group. In conclusion, destruction of glycocalyx was involved in the development of pulmonary hypertension. Pulmonary hypertension can be regulated by protecting the integrity of glycocalyx.
研究领域:
心血管研究
·
肺医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2020
·Vol. 7
·期 21
·2002330
·
IF 15.84
Nan Lyu,Zeyu Du,Hua Qiu,Peng Gao,Qin Yao,Kaiqin Xiong,Qiufen Tu,Xiangyang Li,Binghai Chen,Miao Wang,Guoqing Pan,Nan Huang,Zhilu Yang
Endothelium can secrete vasoactive mediators and produce specific extracellular matrix, which contribute jointly to the thromboresistance and regulation of vascular cell behaviors. From a bionic point of view, introducing endothelium-like functions onto cardiovascular stents represents the most effective means to improve hemocompatibility and reduce late stent restenosis. However, current surface strategies for vascular stents still have limitations, like the lack of multifunctionality, especially the monotony in endothelial-mimic functions. Herein, a layer-by-layer grafting strategy to create endothelium-like dual-functional surface on cardiovascular scaffolds is reported. Typically, a nitric oxide (NO, vasoactive mediator)-generating compound and an endothelial polysaccharide matrix molecule hyaluronan (HA) are sequentially immobilized on allylamine-plasma-deposited stents through aqueous amidation. In this case, the stents could be well-engineered with dual endothelial functions capable of remote and close-range regulation of the vascular microenvironment. The synergy of NO and endothelial glycocalyx molecules leads to efficient antithrombosis, smooth muscle cell (SMC) inhibition, and perfect endothelial cell (EC)-compatibility of the stents in vitro. Moreover, the dual-functional stents show efficient antithrombogenesis ex vivo, rapid endothelialization, and long-term prevention of restenosis in vivo. Therefore, this study will provide new solutions for not only multicomponent surface functionalization but also the bioengineering of endothelium-mimic vascular scaffolds with improved clinical outcomes.
研究领域:
生物医学工程
·
心血管科学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Fanjun Zhang,Yao Xiong,Yage Hu,Jingze Liu,Yuan Wei,Li Yang,Rifang Luo,Yunbing Wang
The endothelial glycocalyx is a natural protective layer for blood vessels. Efficient construction of a reliable glycocalyx-mimetic coating on a vascular implant possesses great potential but remains a challenge. Herein, a novel glycocalyx-mimetic coating featuring the clustered morphology and hydrophilic lubrication is developed via the layer-by-layer self-assembly of polyethyleneimine (PEI) and phosphorylcholine-modified hyaluronic acid (HA-PC). The zwitterionic PC groups in HA-PC exhibited an anti-polyelectrolyte effect to induce the molecular folding and aggregation of HA in solution and enhance its binding capacity to PEI, resulting in an endothelial glycocalyx-mimetic clustered morphology. Besides, zwitterions, rather than hydrophobic groups, can achieve hydrophilic lubrication properties through spatial synergy with HA while inducing the molecular folding of HA, ultimately constructing a glycocalyx-mimetic coating. Such a coating can function well as armor to vascular stent, by virtue of excellent anti-coagulation, anti-inflammation, and endothelial promotion properties in vivo and in vitro. The findings not only provide new insights into the interactions between PC-modified polyelectrolytes but also render a promising glycocalyx-mimetic coating to armor vascular implants.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
血管生物学
✓ 已验证
产品关联
DOI
高影响因子
EXPERIMENTAL NEUROLOGY
·
2020
·
IF 4.691
Xing Li,Jiajia Zhu,Kewei Liu,Yafang Hu,Kaibin Huang,Suyue Pan
Blood brain barrier (BBB) hyperpermeability and brain edema contribute to increased seizure susceptibility and brain injury in status epilepticus (SE). The endothelial glycocalyx is the coating on luminal side of the endothelium and can be considered as the first barrier of BBB. Currently, little is known about the effects of endothelial glycocalyx in SE. We hypothesized glycocalyx degradation could be considered as a first step in the pathophysiology of SE. The study aimed to investigate the impacts of glycocalyx integrity loss on brain damage in a C57BL/6 mouse model of SE induced by lithium-pilocarpine and whether heparin, a competitive antagonist against heparinase , improves survival and neurological outcome. Compared to controls, glycocalyx was significantly degraded after SE, which was mitigated by heparin. The glycocalyx disruption was associated with higher BBB permeability and aggravated brain edema at 72 h after SE, as well as lower survival rate and poorer neurologic outcome. Conversely, preservation of glycocalyx by heparin could reduce SE-induced activation of glia cells , BBB leakage, brain edema, decrease the expressions of inflammatory factors and improve neurologic outcome. The study highlights the importance of glycocalyx degradation in cerebral edema and SE outcome, and indicates heparin treatment may be a new strategy for brain protection in SE.
研究领域:
神经科学
·
药理学
·
神经病学
·
病理生理学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Lei Jin,Xiang Peng,Zeng Shengmei,Chen Le,Zhang Lei,Yuan Zhiyi,Zhang Jun,Wang Tingting,Yu Ruihong,Zhang Wanping,Ibrahim Issa Issoufou,Ma Limei,Yu Chao
Tetramethylpyrazine (TMP), a Chinese traditional herbal extraction widely used in treating cardiovascular diseases, could attenuate vascular endothelial injuries, but the underlying mechanism remains incomprehensive. Vascular glycocalyx coating on the endothelium would be damaged and caused endothelial dysfunction in the inflammatory microenvironment, which was the initial factor of morbidity of many vascular diseases, such as atherosclerosis (AS). Here, we thoroughly investigated the molecular mechanism of TMP on vascular endothelial glycocalyx in the LPS-induced inflammatory model both in vitro and in vivo. Results showed that pretreatment with TMP significantly inhibited glycocalyx degradation and monocytes adhesion to the endothelial process. Moreover, TMP pretreatment inhibited the expression of HPSE1 (a major degrading enzyme of endothelial glycocalyx), Toll-like receptor 4 (TLR4), and the translocation of nuclear factor kappa B p65 (NF-κB p65). We were utilized withTLR4 siRNA, NF-κB inhibitor, and HPSE1 overexpression analysis confirmed TMP’s protection on endothelial glycocalyx injury, which further contributed to the monocyte-endothelial adhesion process. It was indicated that TMP might suppress glycocalyx degradation through TLR4/NF-κB/HPSE1 signaling pathway. Taken together, our results enriched the occurrence molecular mechanism of glycocalyx shedding and molecular regulation mechanism of TMP in protecting integrity of the glycocalyx structure during inflammation. As TMP is currently used in clinical applications, it may be considered a novel strategy against atherosclerosis through its ability to protect endothelial glycocalyx.
研究领域:
心血管疾病
·
分子生物学
·
药理学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Yi Wang,Mengyuan Guo,Peipei Wu,Chong Chen,Weibo Zhang,Fazheng Ren,Pengjie Wang,Shouyun Wu,Jianhuan Wei,Jie Luo,Jinghua Yu
This study provides insights into the composition and in-situ structures of the milk fat globule membrane (MFGM) in buffalo milk with different fat globule sizes (0.55 μm and 8.04 μm). Small fat globules contained a higher amount of MFGM proteins and polar lipids, while the content of MFGM components (except for ADPH) was greater per unit membrane area in large fat globules. A total of 386 differentially expressed proteins were identified, with many of the most differentially expressed proteins being associated with human diseases, such as cancer and elderly diseases. The coverage of sphingomyelin and certain MFGM proteins (BTN and PAS 6/7) on large fat globules was higher, potentially linked to the presence of larger, irregular lipid rafts and patch-shaped glycocalyxes, respectively. These findings suggest that small fat globules are suitable for nutritional fortification of buffalo milk, while large fat globules are appropriate for the preparation of functional dairy-based ingredients.
研究领域:
食品科学
·
营养学
·
生物化学
·
蛋白质组学
·
脂质组学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Xinyi Liang,Aiyang Zhang,Wei Sun,Jiao Lei,Xiaoli Liu,Zengchao Tang,Hong Chen
The endothelial glycocalyx is a carbohydrate–rich layer overlying the outermost surface of endothelial cells. It mediates intercellular interactions by specific chemical compositions (e.g., proteoglycans containing glycosaminoglycan (GAG) side chains) and micro/nanotopography. Inspired by the endothelial glycocalyx, we fabricated a series of glycocalyx–mimetic surfaces with tunable chemical compositions (GAG–like polymers with different functional units) and topographical structures (micro/nanopatterns with pillars different in size). The combination of micro/nanopatterns and GAG–like polymers was flexibly and precisely controlled by replica molding using silicon templates (Si templates) and visible light–initiated polymerization. Human umbilical vein endothelial cells (HUVECs) and human umbilical vein smooth muscle cells (HUVSMCs) were suppressed on surfaces modified with polymers of 2–methacrylamido glucopyranose (MAG) but promoted on surfaces modified with polymers of sodium 4–vinyl–benzenesulfonate (SS) and copolymers of SS and MAG. Surface micro/nanopatterns showed highly complicated effects on surfaces grafted with different GAG–like polymers. Moreover, the spread of HUVSMCs was highly promoted on all flat/patterned surfaces containing sulfonate units, and the elongation effect was stronger on surfaces with smaller pillars. On all the flat/patterned surfaces modified with GAG–like polymers, the adsorption of human vascular endothelial growth factor (VEGF) and human basic fibroblast growth factor (bFGF) was improved, and the amount of VEGF and bFGF absorbed on patterned surfaces containing sulfonate units decreased with pattern dimensions. The decreasing trend of VEGF and bFGF adsorption was in accordance with HUVEC density, suggesting that glycocalyx–mimetic surfaces influence the adsorption of VEGF and bFGF and further influence the growth behavior of vascular cells.
研究领域:
生物材料
·
组织工程
·
细胞生物学
·
生物医学工程
✓ 已验证
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Yu Zhang,Ning Ma,Lu Wang,Liming Liu,Tianze Wang,Hao Liu,Weiping Qian
Heparan sulfate (HS) meshes within the glycocalyx on cell surfaces have protein recognition ability and have been crucial for gaining insights into vital bioprocesses, such as viral infection, cancer development, and inflammation. The protein recognition ability is determined by the mesh property and compositions of HS, although little attention has been paid to the effect of the mesh property on the recognition. An in-depth specificity study of protein-HS-mesh recognition is essential to illustrate related biological functions. Here, ordered porous layer interferometry is applied to study the interaction behavior between mimicked HS meshes and lactoferrin (LF). Our work aimed at mimicking HS meshes with heparin, a widely used substitute of HS, and analyzing the specific LF-heparin-mesh interaction mechanism by inhibiting the nonspecific interaction in a blended sample. We found that the counterion release-based electrostatic interaction is dominant in the specific LF-heparin-mesh recognition. Furthermore, we detail the contributions of nonspecific and specific interactions to the recognition. We illustrate that the concentrated charge distribution of the proteins appears to be primarily related to this robust, specific recognition.
研究领域:
生物化学
·
分子生物学
·
细胞生物学
·
生物物理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Burns & Trauma
·
2021
·
IF 5.099
Liu Lu,Shao Yiming,Zhang Yixuan,Yang Yunxi,Huang Jiamin,Li Linbin,Sun Ran,Zhou Yuying,Su Yicheng,Sun Bingwei
BackgroundBurn shock caused by vascular leakage is one of the main causes of high mortality in severe burn injury. However, the pathophysiological mechanism of vascular leakage is still unclear. The purpose of this study was to explore the molecular mechanism of vascular leakage in the early stage of severe burn and provide a new target for the treatment of severe burns.MethodsNeutrophils were isolated from human peripheral blood by magnetic beads sorting. ELISA was used to detect neutrophil-derived granule proteins and glycocalyx injury products in plasma. The vascular leakage and neutrophil movement were assessed by in vivo laser confocal imaging in mice, and high-quality video were provided. Adhesion-related molecules were investigated by qRT-PCR. The damage to glycocalyx of mice vascular endothelial cells was observed by transmission electron microscope and scanning electron microscope. Proteomic analysis, flow cytometry and immunofluorescence were used to further study the relationship between human peripheral blood neutrophil-derived hypochlorite (HOCl) and CD44 of human vascular endothelial cells.ResultsIn this study, we found that rapidly increasing activated neutrophils secrete heparin binding protein (HBP) and myeloperoxidase (MPO) after severe burn injury. Increased HBP triggers vascular leakage with synergy of MPO, results in systemic edema and burn shock. Furthermore, we found that the MPO catalytic product HOCl but not MPO triggers CD44 extracellular domain shedding from vascular endothelial cells to damage the glycocalyx. Damage to the glycocalyx results in firm adhesion of neutrophils and increases vascular leakage. However, MPO inhibitors partially protect the glycocalyx of vascular endothelial cells. The combination of HBP and MPO inhibitors markedly reduces vascular leakage and systemic edema in the early stage of severe burns.ConclusionsTaken together, these data reveal that neutrophil-derived HBP and MPO play an important synergies role in triggering vascular leakage at the early stage of severe burns. Targeted intervention in these two biomolecules may introduce new strategies for helping to reduce large amount of fluid loss and subsequent burn shock.
研究领域:
免疫学
·
病理生理学
·
烧伤与创伤
·
血管生物学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2021
·
IF 14.593
Qing Ma,Xiuying Shi,Xing Tan,Rui Wang,Kaiqin Xiong,Manfred F. Maitz,Yuanyuan Cui,Zhangmei Hu,Qiufen Tu,Nan Huang,Li Shen,Zhilu Yang
Mimicking the nitric oxide (NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis (ISR) effectively. However, the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx component. Herein, we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species (e.g., Cu-DOTA coordination complex) and glycocalyx-like component (e.g., heparin) to create a durable endothelium-mimicking surface. The stent surface was firstly coated with polydopamine (pDA), followed by a surface chemical cross-link with polyamine (pAM) to form a durable pAMDA coating. Using a stepwise grafting strategy, Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide chemistry. Owing to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules, this proposed strategy could provide 62.4% bioactivity retention ratio of heparin, meanwhile persistently generate NO at physiological level from 5.9 ± 0.3 to 4.8 ± 0.4 × 10 −10 mol cm −2 min −1 in 1 month. As a result, the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis, inflammation, and intimal hyperplasia, enhanced re-endothelialization, and hence efficiently reduced ISR.
研究领域:
生物医学工程
·
材料科学
·
心脏病学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Yan Dai,Jiali Zhang,Shimeng Zhang,Linhua Li,Chao Qu,Jiang Chen,Lei Lu
Bacterial keratitis is a major cause of blindness, hindered by the rising threat of antibiotic resistance. Although corneal bandage lenses (CBLs) are widely utilized in ophthalmic treatment, their effectiveness in treating bacterial keratitis remains limited due to risks of secondary infections, patient discomfort, and complications. In this study, we developed a novel biomimetic coating on CBLs by grafting Ag/Cu bimetallic nanoparticles (Ag/Cu-NPs) and thiol-functionalized heparin (Hep-SH) using a rapid polydopamine (PDA) deposition technique, effectively mimicking the ocular surface glycocalyx structure. The resulting Ag/Cu-NPs/Hep-SH coated CBLs (PNH-CBLs) exhibited significant antibacterial activity, with over 80 % reduction in Staphylococcus aureus ( S. aureus ) and 70 % in Escherichia coli ( E. coli ) due to the sustained release of Ag + and Cu 2+ , along with displaying favorable in vitro biocompatibility. Animal experiments conducted on New Zealand white rabbits with bacterial keratitis demonstrated successful treatment therapeutic outcomes, with PNH-CBLs leading to a significant decrease in clinical score. These biomimetic lenses also exhibited selective anti-protein adsorption properties, minimizing inflammation and promoting surface lubrication. Overall, this innovative approach addresses critical challenges in antibiotic resistance and offers a promising therapeutic strategy for managing ophthalmic infectious diseases.
研究领域:
眼科学
·
纳米技术
·
生物材料
·
抗菌治疗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
·
2023
·
IF 6.7
Yang Wang,Ruiqi Su,Jianwen Chen,Xuan Liu,Jingning Luo,Yaoqiang Lao,Ping Huang,Jinguo Shi,Caibao Jiang,Liping Liao,Jingxia Zhang
Acute ischemic stroke (AIS) is a serious cardiovascular and cerebrovascular disease; Oxidative stress and neuroinflammation are important factors which destroy blood-brain barrier (BBB) in AIS. In the study, a series of 1,3,5-triphenyl-1,2,4-triazole derivatives were designed and synthesized; the optimal compound 9 was obtained by screening their anti-oxidant and anti-inflammatory effects; the neuroprotection effect of compound 9 was evaluated with a rat middle cerebral artery occlusion (MCAO) model. Subsequently, the mechanism of neuroprotection were explored via Western blot. The results prompt compound 9 maybe exert anti-AIS neuroprotection by inhibiting oxidative stress and neuroinflammation inhibition by inhibiting Keap1, COX-2 and iNOS. At the same time, it can protect BBB by reducing glycocalyx degradation and matrix metallopeptidase-9 levels. Its LD 50 > 1000 mg/kg on mice and hERG channel inhibition IC 50 > 30 μM, which lower acute toxicity and hERG channel inhibition would make compound 9 a promising stroke treatment candidate.
研究领域:
药理学
·
神经科学
·
心血管疾病
·
药物发现
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）