ACS Applied Materials & Interfaces
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2016
·
IF 7.145
Hao Chang,Mi Hu,He Zhang,Ke-feng Ren,Bo-chao Li,Huan Li,Li-mei Wang,Wen-xi Lei,Jian Ji
Endothelialization on the vascular implants is of great importance for prevention of undesired postimplantation symptoms. However, endothelial dysfunction of regenerated endothelial cell (EC) monolayer has been frequently observed, leading to severe complications, such as neointimal hyperplasia, late thrombosis, and neoatherosclerosis. It has significantly impeded long-term success of the therapy. So far, very little attention has been paid on endothelial function of EC monolayer. Bioinspired by the microenvironment of the endothelium in a blood vessel, this study described a soft polyelectrolyte multilayer film (PEM) through layer-by-layer assembly of poly(l-lysine) (PLL) and hyaluronan (HA). The (PLL/HA) PEM was chemically cross-linked and further incorporated with vascular endothelial growth factor. It demonstrated that this approach could promote EC adhesion and proliferation, further inducing formation of EC monolayer. Further, improved endothelial function of the EC monolayer was achieved as shown with the tighter integrity, higher production of nitric oxide, and expression level of endothelial function related genes, compared to EC monolayers on traditional substrates with high stiffness (e.g., glass, tissue culture polystyrene, and stainless steel). Our findings highlighted the influence of substrate stiffness on endothelial function of EC monolayer, giving a new strategy in the surface design of vascular implants.
研究领域:
生物材料
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组织工程
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生物医学工程
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2016
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IF 3.902
Hao Chang,He Zhang,Mi Hu,Jia-yan Chen,Bo-chao Li,Ke-feng Ren,M.Cristina L. Martins,Mário A. Barbosa,Jian Ji
Endothelialization has proved to be critical for maintaining long-term success of implantable vascular devices. The formation of monolayer of endothelial cells (ECs) on the implant surfaces is one of the most important factors for the endothelialization. However, endothelial function of regenerated EC monolayer, which plays a much more important role in preventing the complications of post-implantation, has not received enough attention. Here, a vascular endothelial growth factor (VEGF)-incorporated poly( l -lysine)/hyaluronan (PLL/HA) polyelectrolyte multilayer film was fabricated. Through varying the crosslinking degree, stiffness of the film was manipulated, offering either soft or stiff film. We demonstrated that ECs were able to adhere and proliferate on both soft and stiff films, subsequently forming an integrated EC monolayer. Furthermore, endothelial functions were evaluated by characterizing EC monolayer integrity, expression of genes correlated with the endothelial functions, and nitric oxide production. It demonstrated that EC monolayer on the soft film displayed higher endothelial function compared to that on the stiff film. Our study highlights the influence of substrate stiffness on endothelial function, which offers a new criterion for surface design of vascular implants.
研究领域:
生物材料
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组织工程
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
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2024
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IF 3.5
Zhao Jiani,Xiong Yacheng,Liu Yu,Ling Jin,Liu Shuai,Wang Wei
Previous large-scale genetic studies have prioritized the causal genes piezo type mechanosensitive ion channel component 1 ( PIEZO1 ) and castor zinc finger 1 ( CASZ1 ) associated with varicose veins (VVs). This study aims to evaluate their roles in both clinical and experimental VVs. In this study, we investigated abundance of PIEZO1 and CASZ1 in both varicose and normal veins from the same patients. Yoda1 (a selective PIEZO1 agonist, 2.6 mg/kg/day) or vehicle was administered intraperitoneally for 3 weeks to evaluate the effect of PIEZO1 activation on experimental VVs. Subsequently, endothelial Piezo1 deletion mice ( Piezo1 iΔEC mice) were generated to explored the role of endothelial PIEZO1 on VVs. Laser speckle imaging, flow cytometry, cell tracing with Evans blue or rhodamine-6G, and histopathological staining were utilized to evaluate the pathophysiology of VVs. Our results showed that mRNA expression of PIEZO1 , but not CASZ1 , was abundant and increased in clinical VVs. The Piezo1 tP1−td mice revealed endothelium-specific expression of PIEZO1 in mice veins. By establishing iliac vein ligation-induced VVs in mice, Yoda1 exacerbated experimental VVs with increased inflammatory cell infiltration. Subsequently, endothelial Piezo1 deletion ( Piezo1 iΔEC mice) alleviated experimental VVs and vascular remodeling by directly reducing vascular permeability and leukocyte-endothelium interactions compared to the control ( Piezo1 fl/fl mice). PIEZO1 is highly expressed in clinical VVs, meanwhile, activation or inhibition of PIEZO1 exerts a remarkable effect on experimental VVs. Furthermore, Piezo1 may constitute a potential therapeutic approach for the medical treatment of VVs.
研究领域:
心血管疾病
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分子生物学
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实验病理学
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产品关联
DOI
PubMed
高影响因子
Nanomaterials
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2021
·Vol. 11
·期 9
·2334
·
IF 5.076
Yuqing Niu,Massimiliano Galluzzi
In this study, we designed and synthetized artificial vascular scaffolds based on nanofibers of collagen functionalized with hyaluronic acid (HA) in order to direct the phenotypic shape, proliferation, and complete endothelization of mouse primary aortic endothelial cells (PAECs). Layered tubular HA/collagen nanofibers were prepared using electrospinning and crosslinking process. The obtained scaffold is composed of a thin inner layer and a thick outer layer that structurally mimic the layer the intima and media layers of the native blood vessels, respectively. Compared with the pure tubular collagen nanofibers, the surface of HA functionalized collagen nanofibers has higher anisotropic wettability and mechanical flexibility. HA/collagen nanofibers can significantly promote the elongation, proliferation and phenotypic shape expression of PAECs. In vitro co-culture of mouse PAECs and their corresponding smooth muscle cells (SMCs) showed that the luminal endothelialization governs the biophysical integrity of the newly formed extracellular matrix (e.g., collagen and elastin fibers) and structural remodeling of SMCs. Furthermore, in vitro hemocompatibility assays indicated that HA/collagen nanofibers have no detectable degree of hemolysis and coagulation, suggesting their promise as engineered vascular implants.Keywords:collagen;hyaluronic acid;vascular endothelial cells;nanofibers;endothelization
研究领域:
生物材料
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组织工程
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Colloid and Interface Science Communications
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2025
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IF 4.7
Jun Sun,Sulei Zhang,Yichen Wang,Denghai Sheng,Shengjie Liu,Yu Rao,Aiqing Li,Yuchun Pan,John L. Brash,Xiaoli Liu,Hong Chen
Thrombus formation often leads to the failure of intravascular implants. Natural endothelium provides multifaceted antithrombotic functions through nitric oxide/ prostacyclin secretion to inhibit platelet activation, glycosaminoglycan mediated anticoagulation, and tissue-type plasminogen activator driven fibrinolysis. Therefore, surfaces mimicking these multiple endothelial functions are expected to have enhanced antithrombotic properties. In this study, polyvinyl chloride surface was rendered porous through solvent/nonsolvent-induced phase separation and loaded with a metal-organic framework, CuBTTri to catalyze nitric oxide release from a precursor. Furthermore, using layer-by-layer self-assembly, multiple bilayers of a poly(lysine- co -oligo(ethylene glycol) methyl ether methacrylate) copolymer (fibrinolysis-promoting), and sodium heparin (endothelial cell growth-promoting), were deposited on the un-etched side of the polyvinyl chloride. This modified surface was shown to be capable of releasing nitric oxide, destroying nascent thrombus, inhibiting smooth muscle cell growth, and promoting endothelial cell adhesion. This study represents a novel approach to developing multifunctional blood-contacting surfaces that mimic multiple properties of the endothelium.
研究领域:
生物医学工程
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材料科学
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产品关联
DOI
高影响因子
Annals of Dermatology
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2024
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IF 1.5
Lin-Xia Liu,Zhi-Kai Liao,Bing-Qi Dong,Shan Jiang,Tie-Chi Lei
Background Although reports suggest that tranexamic acid (TXA) has clinical benefits for melasma patients by oral, intralesional and topical treatment, the optimal route of TXA therapy and the underlying mechanism involved remain poorly defined. Objective To compare the skin lightening effect between oral TXA and topical TXA and to dissect the molecular mechanisms using ultraviolet B (UVB)-induced hyperpigmentation mouse model, ex vivo cultured human skin explant, and cultured melanocytes (MCs) and endothelial cells. Methods Melanin content and cluster of differentiation 31 (CD31)-positive cell numbers were measured in tail skins from UVB-irradiated mice treated by intragastral or topical TXA using immunofluorescent and Fontana-Masson staining. The conditioned medium (CM) was harvested from human umbilical vein endothelial cells treated with or without 3 mM TXA and was used to treat MCs for 48 hours. mRNA and protein levels of tyrosinase and microphthalmia-associated transcription factor were measured using quantitative real-time reverse transcription polymerase chain reaction and western blotting assays. HMB45- and CD31-positive cell numbers as well as melanin content were also examined in ex vivo cultured human skin explants. Results The hyperpigmented phenotype were significantly mitigated in UVB-irradiated tail skin plus intragastral TXA-treated mice compared with mice treated with UVB only or with UVB plus topical TXA. CD31-positive cell numbers correlated with the anti-melanogenic activity of TXA therapy. The data from cultured cells and skin tissues showed that suppression of endothelin-1 (ET-1) in vascular endothelial cells by TXA reduced melanogenesis and MC proliferation. Conclusion Oral TXA outperforms topical TXA treatment in skin lightening, which contributes to suppression of ET-1 in dermal microvascular endothelial cells by TXA.
研究领域:
皮肤病学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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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
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分子生物学
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药理学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2020
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IF 8.758
Lei Zhang,Feng Wei,Qianqian Bai,Danhong Song,Zhuofan Zheng,Yafei Wang,Xin Liu,AL-Ammari Abdulrahman,Yingxin Bian,Xuran Xu,Chuntao Chen,Hongsong Zhang,Dongping Sun
Despite the widely explored biomaterial scaffolds in vascular tissue engineering applications lately, no ideal platform has been provided for small diameter synthetic vascular grafts mainly due to the thrombosis issue. Endothelium is the only known completely non-thrombogenic material; so, functional endothelialization onto vascular biomaterials is critical in maintaining the patency of vascular networks. Bacterial cellulose (BC) is a natural biomaterial with superior biocompatibility and appropriate hydrophilicity as potential vascular grafts. In previous studies, surface modification of active peptides such as Arg-Gly-Asp (RGD) sequences onto biomaterials has been proven to achieve accelerated and selective endothelial cell (EC) adhesion. In our study, we demonstrated a new strategy to remotely regulate the adhesion of endothelial cells based on an oscillating magnetic field and achieve successful endothelialization on the modified BC membranes. In details, we synthesized bacterial cellulose (BC), magnetic BC (MBC), and RGD peptide-grafted magnetic BC (RMBC), modified with the HOOC-PEG-COOH-coated iron oxide nanoparticles (PEG-IONs). The endothelial cells were cultured on the three materials under different frequencies of an oscillating magnetic field, including “stationary” (0 Hz), “slow” (0.1 Hz), and “fast” (2 Hz) groups. Compared to BC and MBC membranes, the cells on RMBC membranes generally show better adhesion and proliferation. Meanwhile, the “slow” frequency of a magnetic field promotes this phenomenon on RMBC and achieves endothelialization after culture for 4 days, whereas “fast” inhibits the cellular attachment. Overall, we demonstrate a non-invasive and convenient method to regulate the endothelialization process, with promising applications in vascular tissue engineering.
研究领域:
生物医学工程
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组织工程
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2020
·
IF 4.225
Zhao Yixiu,Zhu Jiuxin,Liang Hangfei,Yang Shuang,Zhang Yannan,Han Weina,Chen Chao,Cao Na,Aruhan,Liang Peiqiang,Du Xing,Huang Jian,Wang Jinhui,Zhang Yan,Yang Baofeng
Hypertension is a major risk factor for stroke and cardiovascular events in clinic, which is accompanied by the abnormality of vascular tone and endothelial dysfunction of small artery. Here we report that Kang Le Xin (KLX), a novel anthraquinones compound, could reduce blood pressure and the underlying mechanisms involves that KLX induces endothelium-dependent vasodilation. KLX significantly decreases the arterial blood pressure of spontaneous hypertensive rats (SHR), decreases the contractile reactivity of superior mesenteric artery to phenylephrine and increases the vasodilatory reactivity of superior mesenteric artery to carbachol in a dose-dependent manner. Besides, KLX reduces vascular tension of endothelium-intact mesenteric artery pre-constricted with phenylephrine in a dose-dependent manner, while this effect is inhibited by depriving vascular endothelium or pretreating vascular rings with L-NAME (endothelial nitric oxide synthase inhibitor) or compound C (AMP-activated protein kinase inhibitor). Moreover, KLX increases nitric oxide (NO) generation, endothelial nitric oxide synthase (eNOS), AKT and AMP-activated protein kinase (AMPK) phosphorylation in cultured human umbilical vein endothelial cells (HUVECs), while these effects are inhibited by pretreating cells with compound C. In conclusion, KLX is a new compound with the pharmacological action of reducing arterial blood pressure. The underlying mechanism involves KLX induces endothelium-dependent vasodilation through activating AMPK-AKT-eNOS signaling pathway.
研究领域:
药理学
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心血管科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2019
·
IF 3.973
Chenglong Yu,Meiyi Xing,Shibo Sun,Guoping Guan,Lu Wang
Vascular basement membrane (VBM) is a thin layer of fibrous extracellular matrix linking endothelium, and collagen type IV (COL IV) is its main composition. VBM plays a crucial role in anchoring down the endothelium to its loose connective tissue underneath. For vascular grafts, constructing biomimetic VBMs on the luminal surface is thus an effective approach to improve endothelialization in situ . In the present work, three types of polycaprolactone (PCL) membranes were produced and characterized through cell counting kit-8 (CCK-8) assay, adhesion force and elastic modulus test to examine the influence of fiber diameter and membrane composition on vascular endothelial cell (EC) behaviors. The PCL membranes with finer fibers of 54.77 nm (PCL-54) could biomimic the nanotopography of VBMs more efficiently than 544.64 nm (PCL-544), and they were more suitable for Pig iliac endothelium cells (PIECs) adhesion and proliferation, meanwhile, inducing higher elastic modulus and adhesion force of PIECs. On this foundation, we further immobilized COL IV onto PCL-54 (PCL-COL IV) to biomimic VBMs compositionally. Results showed that PIECs on PCL-COL IV exhibited the highest viability and proliferation. Besides, quantitative data indicated that the elastic modulus of the PIECs on PCL-COL IV (4441.00 Pa) was as two times higher than that on PCL-54 (2312.26 Pa), and the adhesion force grew to 1120.99 pN from 673.58 pN of PIECs on PCL-54. In summary, the PCL-COL IV membranes show high similarity with the native VBMs in terms of structure and composition, suggesting a promising potential for surface modification to vascular grafts for improved endothelialization.
研究领域:
组织工程
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生物材料
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 25
·4017-4029
·
IF 5.047
Shuaibing Jiang,Jingxian Wu,Yingjie Hang,Qi Liu,Dan Li,Hong Chen,John L. Brash
Glycosaminoglycans (GAG) play a vital role in the regulation of various cellular functions through their interactions with key proteins involved in cell signaling and can be useful as bioactive agents in the design of biomaterials. However available “natural” GAG that might be used for this purpose suffer a number of drawbacks including structural heterogeneity and the presence of impurities. Alternatively, GAG-mimicking polymers have shown promise for the modification of biomaterials to support the behavior and function of adherent cells. In the study reported herein, a series of glycopolymers of tailored structure were synthesized using a novel “unit-recombination” strategy. These were intended as surface modifiers for the promotion of surface endothelialization. Two key structural units, sulfonate and saccharide, from the building blocks of GAG, were “recombined” to give GAG analogues by copolymerization of sodium 4-vinylbenzenesulfonate (as the sulfonate unit) and 2-methacrylamido glucopyranose (as the saccharide unit). The composition and molecular weight of the copolymers were adjusted to obtain maximum endothelial cell (EC) proliferation. The glycopolymer with sulfonate and saccharide units in a ratio of approximately 1.0 and a molecular weight of 9.8 kDa was found to be optimal. Interestingly, the data emphasized the key role of saccharide units in GAG bioactivity, rather than the commonly believed decisive role of sulfonate units. The optimized glycopolymer was incorporated into fibrous polycaprolactone (PCL) materials by coaxial electrospinning. These materials showed controlled release of the GAG-mimicking polymers over prolonged periods. The proliferation, migration and function of EC on the glycopolymer-modified PCL fiber mats were greatly improved compared to those on unmodified PCL mats. A likely mechanism underlying these improvements is that the glycopolymers significantly enhance the binding of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) to their receptors on the cell membrane. These findings demonstrate that these structurally-tailored glycopolymers modulate the functions of EC adherent to materials and may be effective as modifiers for the promotion of endothelialization of blood-contacting implants.
研究领域:
生物材料
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组织工程
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细胞生物学
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聚合物化学
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yali Wu,Yunnan Ma,Wanling Zhong,Huijuan Shen,Jinhong Ye,Shouying Du,Pengyue Li
Ethnopharmacological relevance Thrombus generation is one of the leading causes of death in human, and vascular endothelial dysfunction is a major contributor to thrombosis. Pheretima guillemi (Michaelsen), a traditional medicinal animal known as “Dilong”, has been utilized to cure thrombotic disorders for many years. DPf3, a group of functional proteins extracted from P. guillemi , has been characterized and identified to possess antithrombotic bioactivity via in vitro and ex vivo experiments. Aim of the study This study is aimed to investigate the vascular-protection activity and related mechanism of antithrombotic protein DPf3 purified from Pheretima guillelmi systematically. Materials and methods The antithrombotic activity and vascular endothelium protection effect of DPf3 was explored in vivo using ponatinib-induced vascular endothelial injury zebrafish thrombus model. Then, (hi) ox-LDL-induced HUVECs was applied to investigate the protection mechanism of DPf3 against the injury of vascular endothelium. In addition, TMT-based proteomics analysis was used to study the biomarkers, biological processes and signal pathways involved in the antithrombotic and vascular protective effects of DPf3 holistically. Results DPf3 exerted robust in vivo antithrombosis and vascular endothelial protection ability. DPf3 was identified to prevent HUVECs from damage by reducing ROS production, and to reduce monocyte adhesion by decreasing the protein content of adhesion factor VCAM 1. DPf3 was also observed to weaken the migration ability of injured cells and inhibit abnormal angiogenesis. The mechanism of DPf3's antithrombotic and vascular protective activity was mainly related to the regulation of lipid metabolism, energy metabolism, complement and coagulation system, ECM receptor interaction, MAPK signal pathway, etc. Conclusions This study demonstrates that DPf3 has strong antithrombotic and endothelial protective effects. The endothelial protective ability and related mechanisms of DPf3 provide a scientific reference for the traditional use of earthworms in the treatment of thrombosis.
研究领域:
民族药理学
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药理学
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分子生物学
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蛋白质组学
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心血管疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）