Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).T...Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.Methods:A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study.Coronary flow reserve(CFR)was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography.The patients were divided into the following two sub-groups according to CFR:the impaired CFR group with CFR values<2.5 and the preserved CFR group with CFR values≥2.5.Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay.Independent predictors for impaired CFR were identified by binary logistic regression analysis.The receiveroperating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.Results:We found that age,percentage of female sex,N-terminal pro-B-type natriuretic peptide levels,Ang-2 levels(763.3±264.9 vs.579.7±169.3 pg/mL,P<0.001),and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR.Serum Ang-2 levels were negatively correlated with CFR(r=0.386,P<0.001).Binary logistic regression analysis showed that Ang-2(odds ratio:1.004,95%confidence interval[CI]:1.001–1.006,P=0.003)and age(odds ratio:1.088,95%CI:1.023–1.156,P=0.007)were independently associated with impaired CFR.Furthermore,Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve(P<0.001).The area under the curve was 0.712(95%CI:0.612–0.813).Conclusions:High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.展开更多
Background and aim:Severe alcoholic hepatitis(SAH),the most florid form of alcohol-related liver dis-ease(ALD),has a mortality rate of 16%at 28 days.The angiopoietin-Tie 2 system regulates angiogenesis and inflammatio...Background and aim:Severe alcoholic hepatitis(SAH),the most florid form of alcohol-related liver dis-ease(ALD),has a mortality rate of 16%at 28 days.The angiopoietin-Tie 2 system regulates angiogenesis and inflammation,both of which are implicated in the pathogenesis of ALD.This study examined plasma and hepatic gene expression of angiopoietin 1(ANG1)and angiopoietin 2(ANG2)in patients with SAH and ALD and investigated their roles as prognostic biomarkers.Methods:A case-control study was performed measuring plasma levels of ANG1 and ANG2 by enzyme-linked immunosorbent assay(ELISA)from 30 patients with SAH(Maddrey's discriminant function32),32 patients with ALD cirrhosis and 15 healthy controls(HC).RNA sequencing for ANG1,ANG2,TIE1(codes for Tie1 receptor)and TEK(codes for Tie2 receptor)gene expression from a separate cohort study of 79 patients was also performed.Results:Plasma levels of ANG1 were lower(P=0.010)and ANG2 were higher(P<0.0001)in patients with ALD/SAH compared to HC.The ANG2:ANG1 ratio was higher in those with ALD/SAH compared to HC(P<0.0001).ANG2 levels were the highest in patients who developed sepsis(P=0.030)and those dying within 90 days(P=0.020).ANG2 levels correlated positively with model for end-stage liver disease(MELD)score(r=0.30,P=0.020),Child-Pugh score(r=0.38,P=0.003),international normalized ratio(r=0.41,P=0.001)and white blood cell count(r=0.28,P=0.040)and inversely correlated with albumin(r=0.26,P=0.040).ANG1 gene expression from liver biopsies was higher in SAH than that in HC(P<0.0001),and greater in severe disease(P<0.0001).ANG2 gene expression trended towards being lower in SAH than that in HC(P=0.070)though was upregulated in severe disease(P=0.0003).Conclusions:Plasma ANG2 is raised in SAH and ALD and could be useful as a prognostic biomarker in this patient population.展开更多
目的:观察血管生成素-2(angiopoietin-2)和金属基质蛋白酶-9(MMP-9)在胃癌组织中的表达,并探讨其临床意义. 方法:用免疫组化染色法检测了50例胃癌患者癌组织, 10例非癌胃黏膜组织中angiopoietin-2(Ang-2),MMP-9, CD-34蛋白的表达. 结果...目的:观察血管生成素-2(angiopoietin-2)和金属基质蛋白酶-9(MMP-9)在胃癌组织中的表达,并探讨其临床意义. 方法:用免疫组化染色法检测了50例胃癌患者癌组织, 10例非癌胃黏膜组织中angiopoietin-2(Ang-2),MMP-9, CD-34蛋白的表达. 结果:胃癌组织中Ang-2,MMP-9的阳性率分别为56% 和60%,显著高于非癌胃黏膜.他们的表达水平与胃癌的分化程度呈负相关(25% vs 71%,X2=9.18,P<0.01; 31% vs 74%,X2=8.10,P<0.01),与肿瘤的TNM分期(30% vs 78%,P<0.01:35% vs 81%,P<0.01),淋巴结转移(39% vs 70%,P<0.05;43% vs 74%,P<0.05),微血管密度(Ang-2:74.9±11.8 vs 65.6±11.5,P<0.05)成正相关(此外,MMP-9的表达水平还与肿瘤浸润的深度成正相关(33% vs 79%,X2=10.73,P<0.01).Ang-2、MMP-9 在胃癌中的阳性表达率之间存在一定相关性(X2=3.0, P<0.01). 结论:Ang-2、MMP-9在胃癌的侵袭与转移中起重要作用,并且他们之间存在相互诱导或是协同效应,其共位表达可作为判断预后的指标.展开更多
Ephrin-B2 has been shown to participate in angiogenesis, but the underlying mechanisms involved remain unclear. In this study, a rat model of local cerebral ischemia was prepared by focal middle cerebral artery occlus...Ephrin-B2 has been shown to participate in angiogenesis, but the underlying mechanisms involved remain unclear. In this study, a rat model of local cerebral ischemia was prepared by focal middle cerebral artery occlusion, followed by 24-hour reperfusion. Then, ephrin-B2 protein was administered intracerebroventricularly for 3 consecutive days via a micro-osmotic pump. Western blot assay and quantitative real-time reverse transcription PCR demonstrated the expression levels of angiopoietin-1 （Ang-1） mRNA and protein in the penumbra cortex of the ephrin-B2 treated group were decreased at day 4 after reperfusion, and increased at day 28, while the expression levels of angiopoietin-2 （Ang-2） were highly up-regulated at all time points tested. Double immunofluorescent staining indicated that Ang-1 and Ang-2 were both expressed in vascular endothelial cells positive for CD31. These findings indicate that ephrin-B2 influences the expressions of Ang-1 and Ang-2 during angiogenesis following transient focal cerebral ischemia.展开更多
To explore the relationship of angiogenesis-related angiopoietin-2 gene and its receptor Tie2 with angiogenesis and the biology of hepatocellular carcinoma (HCC), angiopoietin-2 gene, Tie2 and CD34 protein expression ...To explore the relationship of angiogenesis-related angiopoietin-2 gene and its receptor Tie2 with angiogenesis and the biology of hepatocellular carcinoma (HCC), angiopoietin-2 gene, Tie2 and CD34 protein expression in 22 resected HCC, 8 cirrhotic and 8 control liver specimens were investigated by in situ hybridization and immunohistochemistry respectively, and the level of angiopoietin-2 and Tie2 expression in HCC were compared in terms of tumor biological parameters. It was found that CD34 was not expressed in control liver, expressed scarcely in cirrhotic liver (17 8±13 5/HP), but intensively expressed in HCC (86. 3±34. 8/HP, P<0. 01). Tie2 receptor was not expressed in controls, expressed at low level in cirrhotic liver (11. 3±8. 7/HP), while strongly positive in the microvascular endothelia of HCC (52. 4±16. 7/HP, P<0. 01). The level of Tie2 receptor expression in HCC was closely related with tumor diameter, angiogenesis and portal invasion. Angiopoietin-2 gene was not expressed in control liver, expressed mildly in cirrhotic liver (11. 2±9. 7/HP), but extensively in tumor zone (36. 4±17. 5/HP), the level of angiopoietin-2 expression was closely related with angiogenesis, portal invasion and histological grading of HCC. It is concluded that angiogenesis is increased in HCC; angiopoietin-2/Tie2 expression in human hepatic carcinoma is closely related with angiogenesis, which are probably involved in the HCC angiogenesis regulation, promoting the development and metastasis of human hepatic cancer.展开更多
文摘目的:探讨检测血管内皮生长因子(vascular endothelial growth factor,VEGF)及血管生成素-2(An-giopoietin-2,Ang-2)对恶性胸腔积液的诊断价值。方法:选择恶性胸腔积液患者31例,良性胸腔积液3例,(ROC)曲线计算上述指标的诊断敏感度、特异度及ROC曲线下面积。并对VEGF及Ang-2之间的相关性进行分析。结果:恶性胸腔积液中的VEGF及Ang-2含量(1106±555 vs 527±229,19.26±6.39 vs 12.25±7.1)明显高于良性胸腔积液(P<0.05);VEGF诊断恶性胸腔积液的敏感度及特异度分别是:82%和90%,Ang-2诊断的敏感度及特异度分别是:65%和71%;恶性胸腔积液中Ang-2的含量与VEGF的含量呈正相关。结论:VEGF及Ang-2可作为恶性胸腔积液诊断的良好指标,可指导选择对患者进行进一步的侵入性检查。
基金This work was supported by grants from the National Natural Sciences Foundation of China(No.81400177)Natural Science Foundation of Beijing Municipality(No.7154249).
文摘Background:Angiopoietin-2(Ang-2)is a type of endothelial growth factor involved in angiogenesis and vascular remodeling.Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease(CAD).This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.Methods:A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study.Coronary flow reserve(CFR)was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography.The patients were divided into the following two sub-groups according to CFR:the impaired CFR group with CFR values<2.5 and the preserved CFR group with CFR values≥2.5.Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay.Independent predictors for impaired CFR were identified by binary logistic regression analysis.The receiveroperating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.Results:We found that age,percentage of female sex,N-terminal pro-B-type natriuretic peptide levels,Ang-2 levels(763.3±264.9 vs.579.7±169.3 pg/mL,P<0.001),and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR.Serum Ang-2 levels were negatively correlated with CFR(r=0.386,P<0.001).Binary logistic regression analysis showed that Ang-2(odds ratio:1.004,95%confidence interval[CI]:1.001–1.006,P=0.003)and age(odds ratio:1.088,95%CI:1.023–1.156,P=0.007)were independently associated with impaired CFR.Furthermore,Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve(P<0.001).The area under the curve was 0.712(95%CI:0.612–0.813).Conclusions:High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.
文摘Background and aim:Severe alcoholic hepatitis(SAH),the most florid form of alcohol-related liver dis-ease(ALD),has a mortality rate of 16%at 28 days.The angiopoietin-Tie 2 system regulates angiogenesis and inflammation,both of which are implicated in the pathogenesis of ALD.This study examined plasma and hepatic gene expression of angiopoietin 1(ANG1)and angiopoietin 2(ANG2)in patients with SAH and ALD and investigated their roles as prognostic biomarkers.Methods:A case-control study was performed measuring plasma levels of ANG1 and ANG2 by enzyme-linked immunosorbent assay(ELISA)from 30 patients with SAH(Maddrey's discriminant function32),32 patients with ALD cirrhosis and 15 healthy controls(HC).RNA sequencing for ANG1,ANG2,TIE1(codes for Tie1 receptor)and TEK(codes for Tie2 receptor)gene expression from a separate cohort study of 79 patients was also performed.Results:Plasma levels of ANG1 were lower(P=0.010)and ANG2 were higher(P<0.0001)in patients with ALD/SAH compared to HC.The ANG2:ANG1 ratio was higher in those with ALD/SAH compared to HC(P<0.0001).ANG2 levels were the highest in patients who developed sepsis(P=0.030)and those dying within 90 days(P=0.020).ANG2 levels correlated positively with model for end-stage liver disease(MELD)score(r=0.30,P=0.020),Child-Pugh score(r=0.38,P=0.003),international normalized ratio(r=0.41,P=0.001)and white blood cell count(r=0.28,P=0.040)and inversely correlated with albumin(r=0.26,P=0.040).ANG1 gene expression from liver biopsies was higher in SAH than that in HC(P<0.0001),and greater in severe disease(P<0.0001).ANG2 gene expression trended towards being lower in SAH than that in HC(P=0.070)though was upregulated in severe disease(P=0.0003).Conclusions:Plasma ANG2 is raised in SAH and ALD and could be useful as a prognostic biomarker in this patient population.
文摘目的:观察血管生成素-2(angiopoietin-2)和金属基质蛋白酶-9(MMP-9)在胃癌组织中的表达,并探讨其临床意义. 方法:用免疫组化染色法检测了50例胃癌患者癌组织, 10例非癌胃黏膜组织中angiopoietin-2(Ang-2),MMP-9, CD-34蛋白的表达. 结果:胃癌组织中Ang-2,MMP-9的阳性率分别为56% 和60%,显著高于非癌胃黏膜.他们的表达水平与胃癌的分化程度呈负相关(25% vs 71%,X2=9.18,P<0.01; 31% vs 74%,X2=8.10,P<0.01),与肿瘤的TNM分期(30% vs 78%,P<0.01:35% vs 81%,P<0.01),淋巴结转移(39% vs 70%,P<0.05;43% vs 74%,P<0.05),微血管密度(Ang-2:74.9±11.8 vs 65.6±11.5,P<0.05)成正相关(此外,MMP-9的表达水平还与肿瘤浸润的深度成正相关(33% vs 79%,X2=10.73,P<0.01).Ang-2、MMP-9 在胃癌中的阳性表达率之间存在一定相关性(X2=3.0, P<0.01). 结论:Ang-2、MMP-9在胃癌的侵袭与转移中起重要作用,并且他们之间存在相互诱导或是协同效应,其共位表达可作为判断预后的指标.
文摘Ephrin-B2 has been shown to participate in angiogenesis, but the underlying mechanisms involved remain unclear. In this study, a rat model of local cerebral ischemia was prepared by focal middle cerebral artery occlusion, followed by 24-hour reperfusion. Then, ephrin-B2 protein was administered intracerebroventricularly for 3 consecutive days via a micro-osmotic pump. Western blot assay and quantitative real-time reverse transcription PCR demonstrated the expression levels of angiopoietin-1 （Ang-1） mRNA and protein in the penumbra cortex of the ephrin-B2 treated group were decreased at day 4 after reperfusion, and increased at day 28, while the expression levels of angiopoietin-2 （Ang-2） were highly up-regulated at all time points tested. Double immunofluorescent staining indicated that Ang-1 and Ang-2 were both expressed in vascular endothelial cells positive for CD31. These findings indicate that ephrin-B2 influences the expressions of Ang-1 and Ang-2 during angiogenesis following transient focal cerebral ischemia.
文摘To explore the relationship of angiogenesis-related angiopoietin-2 gene and its receptor Tie2 with angiogenesis and the biology of hepatocellular carcinoma (HCC), angiopoietin-2 gene, Tie2 and CD34 protein expression in 22 resected HCC, 8 cirrhotic and 8 control liver specimens were investigated by in situ hybridization and immunohistochemistry respectively, and the level of angiopoietin-2 and Tie2 expression in HCC were compared in terms of tumor biological parameters. It was found that CD34 was not expressed in control liver, expressed scarcely in cirrhotic liver (17 8±13 5/HP), but intensively expressed in HCC (86. 3±34. 8/HP, P<0. 01). Tie2 receptor was not expressed in controls, expressed at low level in cirrhotic liver (11. 3±8. 7/HP), while strongly positive in the microvascular endothelia of HCC (52. 4±16. 7/HP, P<0. 01). The level of Tie2 receptor expression in HCC was closely related with tumor diameter, angiogenesis and portal invasion. Angiopoietin-2 gene was not expressed in control liver, expressed mildly in cirrhotic liver (11. 2±9. 7/HP), but extensively in tumor zone (36. 4±17. 5/HP), the level of angiopoietin-2 expression was closely related with angiogenesis, portal invasion and histological grading of HCC. It is concluded that angiogenesis is increased in HCC; angiopoietin-2/Tie2 expression in human hepatic carcinoma is closely related with angiogenesis, which are probably involved in the HCC angiogenesis regulation, promoting the development and metastasis of human hepatic cancer.
