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World Journal of Gastroenterology 2023年第24期29卷 3748-3757页

作者： Yun Jin Ying-Hao Guo Jia-Cheng Li Qi Li Dan Ye Xiao-Xiao Zhang Jiang-Tao Li Department of Hepatopancreatobiliary Surgery The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310009Zhejiang ProvinceChina Department of General Surgery Yuhuan Second People’s HospitalTaizhou 317600Zhejiang ProvinceChina

Partial hepatectomy(PH)can lead to severe complications,including liver failure,due to the low regenerative capacity of the remaining liver,especially after extensive hepatectomy.Liver sinusoidal endothelial cells(LSECs),whose proliferation occurs more slowly and later than hepatocytes after PH,compose the lining of the hepatic sinusoids,which are the smallest blood vessels in the liver.vascular endothelial growth factor(VEGF),secreted by hepatocytes,promotes LSEC proliferation.Supplementation of exogenous VEGF after hepatectomy also increases the number of LSECs in the remaining liver,thus promoting the reestablishment of the hepatic sinusoids and accelerating liver regeneration.At present,some shortcomings exist in the methods of supplementing exogenous VEGF,such as a low drug concentration in the liver and the reaching of other organs.Moreover,VEGF should be administered multiple times and in large doses because of its short half-life.This review summarized the most recent findings on liver regeneration and new strategies for the localized delivery VEGF in the liver.

关键词： Liver regeneration vascular endothelial growth factor Nano materials Liver resection

vascular endothelial growth factor gene polymorphisms in age-related macular degeneration in a Turkish population

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International Journal of Ophthalmology(English edition) 2014年第5期7卷 773-777页

作者： Yunus Bulgu Gokhan Ozan Cetin Vildan Caner Ebru Nevin Cetin Volkan Yaylali Cem Yildirim Department of Ophthalmology School of MedicinePamukkale University Department of Medical Genetics School of MedicinePamukkale University Department of Medical Biology School of MedicinePamukkale University

AIM:To assess the association between age-related macular degeneration(AMD) and three single nucleotide polymorphisms(SNPS) related to the vascular endothelial growth factor(VEGF) gene.METHODS:The patients who were diagnosed with AMD were included in this prospective study. Three SNPs(rs1413711, rs2146323, and rs3025033) of the VEGF gene were genotyped by real-time polymerase chain reaction in the genomic DNA isolated from peripheral blood samples of the 82 patients and 80 controls.RESULTS:The genotype frequencies of rs1413711 and rs2146323 were not significantly different between the study group and the control group(P =0.072 and P =0.058).However, there was a significant difference in the genotype frequencies of these SNPs between the wet type AMD and dry type AMD(P =0.005 and P =0.010,respectively). One of the SNPs(rs1413711) was also found to be associated with the severity of AMD(P =0.001)with significant genotype distribution between early,intermediate, and advanced stages of the disease. The ancestral alleles were protective for both SNPs while the polymorphic alleles increased the risk for dry AMD.CONCLUSION:VEGF SNPs rs1413711 and rs2146323 polymorphisms are significantly associated with AMD subtypes in our population.

关键词： age-related macular degeneration vascular endothelial growth factor single nucleotide polymorphism

vascular endothelial growth factor up-regulates the expression of intracellular adhesion molecule-1 in retinal endothelial cells via reactive oxygen species, but not nitric oxide

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Chinese Medical Journal 2009年第3期122卷 338-343页

作者： ZHANG Xiao-ling WEN Liang CHEN Yan-jiong ZHU Yi Department of Ophthalmology First Affiliated Hospital Xi'anJiaotong University School of Medicine Xi'an Shaanxi 710061China Department of Immunology and Microbiology Xi'an JiaotongUniversity School of Medicine Xi'an Shaanxi 710061 China Department of Physiology and Pathophysiology Peking UniversityHealth Science Center Beijing 100083 China

Background The vascular endothelial growth factor （VEGF） is involved in the initiation of retinal vascular leakage and nonperfusion in diabetes. The intracellular adhesion molecule-1 （ICAM-1） is the key mediator of the effect of VEGFs on retinal leukostasis. Although the VEGF is expressed in an early-stage diabetic retina, whether it directly up-regulates ICAM-1 in retinal endothelial cells （ECs） is unknown. In this study, we provided a new mechanism to explain that VEGF does up-regulate the expression of ICAM-1 in retinal ECs. Methods Bovine retinal ECs （BRECs） were isolated and cultured. Immunohistochemical staining was performed to identify BRECs. The cultured cells were divided into corresponding groups. Then, VEGF （100 ng/ml） and other inhibitors were used to treat the cells. Cell lysate and the cultured supernatant were collected, and then, the protein level of ICAM-1 and phosphorylation of the endothelial nitric oxide synthase （eNOS） were detected using Western blotting. Griess reaction was used to detect nitric oxide （NO）. Results Western blotting showed that the VEGF up-regulated the expression of ICAM-1 protein and increased phosphorylation of the eNOS in retinal ECs. Neither the block of NO nor protein kinase C （PKC） altered the expression of ICAM-1 or the phosphorylation of eNOS. The result of the Western blotting also showed that inhibition of phosphatidylinositol 3-kinase （PI3K） or reactive oxygen species （ROS） significantly reduced the expression of ICAM-1. Inhibition of PI3K also reduced phosphorylation of eNOS. Griess reaction showed that VEGF significantly increased during NO production. When eNOS was blocked by L-NAME or PI3K was blocked by LY294002, the basal level of NO production and the increment of NO caused by VEGF could be significantly decreased. Conclusion ROS-NO coupling in the retinal endothelium may be a new mechanism that could help to explain why VEGF induces ICAM-1 expression and the resulting leukostasis in diabetic retinopathy.

关键词： vascular endothelial growth factor intercellular adhesion molecule-1 reactive oxygen species,＂endothelial nitric oxide synthase phosphatidylinositol 3-kinase

vascular endothelial growth factor/platelet-derived growth factor receptor pathway is involved in bone marrow mesenchymal stem cell differentiation and directional migration toward gliomas

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Neural Regeneration Research 2010年第13期5卷 993-998页

作者： Chaoshi Niu Yongfei Dong Ge Gao Department of Neurosurgery Anhui Provincial Hospital of Anhui Medical University Hefei 230001 Anhui Province China Molecular Neurobiology & Neural Regeneration and Repairing Laboratory Anhui Provincial Stereotactic Neurosurgical Institute Hefei 230001 Anhui Province China

BACKGROUND： vascular endothelial growth factor （VEGF） induces bone marrow-derived mesenchymal stem cell （BMSC） differentiation into vascular endothelial-like cells and promotes BMSC migration toward gliomas. However, the molecular mechanisms by which VEGF induces BMSC differentiation and migration remain poorly understood. OBJECTIVE; To investigate the role of platelet-derived growth factor （PDGF） receptor （PDGFR） in BMSC differentiation and migration induced by VEGE DESIGN, TIME AND SETTING： A parallel, controlled, in vitro experiment was performed at the Molecular Neurobiology ＆ Neural Regeneration and Repairing Laboratory, Anhui Provincial Hospital of Anhui Medical University, China from June 2008 to March 2009. MATERIALS： U87 glioma cells were purchased from Shanghai Institutes for Biological Sciences; mouse anti-human PDGFR and VEGF receptor （VEGFR） monoclonal antibodies were purchased from Peprotech, USA. METHODS： Isolated BMSCs were precultured with neutralizing antibody for VEGFR-1, VEGFR-2, PDGFR-α, and PDGFR-β to block biological activity of related receptors, followed by induced differentiation with 50μg/L VEGF. BMSCs induced with 50μg/L VEGF alone served as the VEGF-induced group. The control group remained untreated. MAIN OUTCOME MEASURES： Cell surface markers were identified by flow cytometry; BMSC surface cytokine receptor expression was detected by reverse transcription-polymerase chain reaction; the Transwell model was used to observe cell migration. RESULTS： After blocking the PDGFR, VEGF did not induce BMSC cell surface marker CD-31 or von Willebrand factor （vWF） expression. However, inhibition with VEGF receptor blocking agents, VEGF induced BMSCs to express CD-31 and vWE Following inhibition of the PDGFR, the number of cells migrating through the polycarbonate membrane Transwell chamber was decreased, as well as the number of BMSCs migrating to glioma cells. However, through the use of VEGF receptor blocking agents, the number of migrating cells remained unchanged. VEGF preculture increased t

关键词： vascular endothelial growth factor platelet-derived growth factor receptor bone marrow-derived mesenchymal stem cells glioma immunofluorescence

vascular endothelial growth factor expressing mesen-chymal stem cells improves cardiac function in chronic myocardial infarction in pigs

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Chinese Medical Journal 2006年第19期119卷 1664-1668页

作者： YI Fu GUO Wen-yi Lue An-lin WANG Hai-chang LI Hu LI Wei-jie LIU Bing ZHANG Dian-xin LUAN Rong-hua CHENG He-xiang LI Fei QIN Tao ZHAO Zhi-jing GAO Feng JIA Guo-liang Department of Cardiology Xijing Hospital Fourth Military Medical University Xi＇an 710032 China Department of Physiology Fourth Military Medical University Xi＇ an 710032 China

Transplantation of mesenchymal stem cells （MSCs） for myocardial reconstruction has shown promise in both animal models and human phase 1 clinical studies. vascular endothelial growth factor （VEGF） is a strong therapeutic agent for treating ischaemia by inducing angiogenesis. The feasibility of ex vivo MSCs mediated gene transfer is documented. Matsumoto and colleagues have recently reported genetically engineered MSCs carrying VEGF165 delivery for revascularization in a model of acute myocardial infarction （MI）. The promising data from our laboratory in both angiogenesis and MSCs transplantation in cunicular heart model of acute MI have prompted us to attempt the combined and simultaneous application of the two strategies.

关键词： myocardial infarction mesenchymal stem cell transplantation vascular endothelial growth factor ventricular function

Overexpression of vascular endothelial growth factor enhances the neuroprotective effects of bone marrow mesenchymal stem cell transplantation in ischemic stroke

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Neural Regeneration Research 2023年第6期18卷 1286-1292页

作者： Cui Liu Zhi-Xiang Yang Si-Qi Zhou Ding Ding Yu-Ting Hu Hong-Ning Yang Dong Han Shu-Qun Hu Xue-Mei Zong Institute of Emergency Rescue Medicine Emergency Centerthe Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina Emergency Department of Affiliated Lianyungang Hospital of Xuzhou Medical University/The First People’s Hospital of Lianyungang LianyungangLianyungangJiangsu ProvinceChina Laboratory of Emergency Medicine Second Clinical Medical College of Xuzhou Medical UniversityXuzhou Medical UniversityXuzhouJiangsu ProvinceChina Key Laboratory of Brain Diseases Bioinformation Xuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

关键词： bone marrow mesenchymal stem cell brain-derived neurotrophic factor CD31 microtubule associated protein 2 middle cerebral artery occlusion stroke transplantation vascular endothelial growth factor

Sustained delivery of vascular endothelial growth factor mediated by bioactive methacrylic anhydride hydrogel accelerates peripheral nerve regeneration after crush injury

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Neural Regeneration Research 2022年第9期17卷 2064-2071页

作者： Wanlin Xu Yifan Wu Hao Lu Yun Zhu Jinhai Ye Wenjun Yang Department of Oral and Maxillofacial-Head and Neck Oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyShanghaiChina Jiangsu Key Laboratory of Oral Diseases Department of Oral and Maxillofacial SurgeryThe Affiliated Stomatological Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina

Neurotrophic factors,currently administered orally or by intravenous drip or intramuscular injection,are the main method for the treatment of peripheral nerve crush injury.However,the low effective drug concentration arriving at the injury site results in unsatisfactory outcomes.Therefore,there is an urgent need for a treatment method that can increase the effective drug concentration in the injured area.In this study,we first fabricated a gelatin modified by methacrylic anhydride hydrogel and loaded it with vascular endothelial growth factor that allowed the controlled release of the neurotrophic factor.This modified gelatin exhibited good physical and chemical properties,biocompatibility and supported the adhesion and proliferation of RSC96 cells and human umbilical vein endothelial cells.When injected into the epineurium of crushed nerves,the composite hydrogel in the rat sciatic nerve crush injury model promoted nerve regeneration,functional recovery and vascularization.The results showed that the modified gelatin gave sustained delivery of vascular endothelial growth factors and accelerated the repair of crushed peripheral nerves.

关键词： bioactive material controlled release crush injury hydrogel muscle function nerve regeneration peripheral nerve sciatic function index vascular endothelial growth factor vascularization

vascular endothelial growth factor gene transfection to enhance the repair of avascular necrosis of the femoral head of rabbit

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Chinese Medical Journal 2003年第10期116卷 1544-1548页

作者：杨操杨述华杜靖远李进许伟华熊宇芳 Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science & Technology Department of Biochemistry Tongji Medical CollegeHuazhong University of Science & Technology

Objective To explore a new method for the therapy of avascular necrosis of the femoral head. Methods The recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head. The expression of vascular endothelial growth factor (VEGF) was examined by RNA dot hybridization and immunohistochemical techniques. Repair of the femoral head was observed by histological and histomorphometric analysis.Results The expression of VEGF was detected in the femoral head transfected with the VEGF gene. The femoral head transfected with the VEGF gene showed a significant increase in angiogenesis 2 and 4 weeks after gene transfection and a significant increase in bone formation 6 and 8 weeks after gene transfection on histomorphometric analysis ( P <0.01).Conclusions Transfection of the VEGF gene enhances bone tissue angiogenesis. Repair of osteonecrosis could be accelerated accordingly,thus providing a potential method for therapy of osteonecrosis.

关键词： vascular endothelial growth factor gene transfection avascular necrosis femoral head

Low expression of vascular endothelial growth factor and high serum level of cyclic guanine monophosphate as the risk factors of femoral head osteonecrosis in alcohol-exposed Wistar rat

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Chinese Journal of Traumatology 2020年第2期23卷 107-112页

作者： I Ketut Suyasa Anak Agung Wiradewi Lestari Department of Orthopedic and Traumatology Faculty of MedicineUdayana UniversityBaliIndonesia Department of Clinical Pathology Faculty of MedicineUdayana UniversityBaliIndonesia

Purpose:Severe damage to the femoral head in patients with osteonecrosis has a high impact on morbidity.Despite early diagnosis,the treatment outcome is still unsatisfactory.This study aimed to explore the expression of vascular endothelial growth factor(VEGF)and cyclic guanine monophosphate(cGMP)serum level as the risk factors of femoral head osteonecrosis in alcohol-exposed Wistar rats.Methods:This was an exper imental study using randomized post-test only control group design,with samples using 10-14 weeks Wistar male rats.Rats were then divided into 6 groups:3 groups without intervention,and 3 groups with intervention using 40%alcohol given perorally.Each one group from intervention and control group was euthanized by the end of the week for 3 consecutive weeks.Proximal femurs were examined under microscope for osteonecrosis,immunohistochemically for VEGF,and blood serum for cGMP levels.Results:VEGF expression in the femoral head of alcohol-exposed Wistar rats was lower than those not exposed to alcohol(p<0.005).Blood serum cGMP levels of alcohol-exposed Wistar rats were higher than those not exposed to alcohol(p<0.005).The number of necrotic osteocytes in the femoral head of Wistar rats exposed to alcohol was greater than those not exposed to alcohol(p<0.005).There are significant differences between VEGF,cGMP levels,and number of necrotic osteocytes in the control group and treatment at 1st,2nd'and 3rd week(p<0.005).Conclusions:Based on the result of this study,VEGF and cGMP may be considered as diagnostic bio-markers for alcohol-induced femoral head osteonecrosis.

关键词： Cyclic guanosine monophosphate Osteonecrosis vascular endothelial growth factor

In Vitro Angiogenesis Effect of Xuefu Zhuyu Decoction(血府逐瘀汤)and vascular endothelial growth factor:A Comparison Study

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Chinese Journal of Integrative Medicine 2018年第8期24卷 606-612页

作者： LIN Fan CHEN Bin-ling WANG Yi-zheng GAO Dong SONG Jun T.J.Kaptchuk CHEN Ke-ji College of Integrative Medicine Fujian University of Traditional Chinese MedicineFuzhou 350122China The Second Hospital of Longyan LongyanFujian Province 364000China Experimental Research Center China Academy of Chinese Medical SciencesBeijing 100700China Beth Israel Deaconess Medical Center Harvard Medical SchoolBostonMA 02215USA Xiyuan Hospital China Academy of Chinese Medical SciencesBeijing 100091China

Objective： To compare the angiogenesis behaviors of vascular endothelial growth factor（VEGF） and Chinese medicine Xuefu Zhuyu Decoction（血府逐瘀汤,XZD） treatments.Methods： Human microvascular endothelial cells（HMEC-1） were treated with various concentrations of either XZD-containing serum（XZD-CS） or VEGF for 24,48,and 72 h,respectively.Cell viability,proliferation,migration,adhesion,and in vitro tube formation assays were used to assess their angiogenic effects.Results： VEGF promoted all cellular phases involved in angiogenesis including cell viability,proliferation,migration,adhesion,and tube formation（P〈0.05 or P〈0.01）.Unlike the continuous promotion effects of VEGF at the above stages,XZD inhibited cell viability and proliferation（P〈0.05 or P〈0.01） and only promoted tube formation in the early phase of angiogenesis（P〈0.01）.Conclusions： These two medications promote different angiogenesis behaviors,which might be an important reason for their distinct therapeutic profile in clinical usage.

关键词： Xuefu Zhuyu Decoction Chinese medicine vascular endothelial growth factor angiogenesis