Objective： To explore angiopoietins （Ang-1, Ang-2）/Tie-2 expression and angiogenesis in stomach carcinomas. Methods： RT-PCR and immunohistochemistry were used to detect angiopoietins/Tie- 2 mRNA and protein expres...Objective： To explore angiopoietins （Ang-1, Ang-2）/Tie-2 expression and angiogenesis in stomach carcinomas. Methods： RT-PCR and immunohistochemistry were used to detect angiopoietins/Tie- 2 mRNA and protein expression in stomach carcinomas and their adjacent normal mucosa. Microvessel density （MVD） was counted according to CD34 immunohistochemical staining. Results： There was positive expression of Angiopoietins/Tie-2 mRNA and protein in stomach carcinomas and their paired adjacent normal mucosa. It was found that correlation between Ang-1 protein, Tie-2 mRNA expression and MVD was negative （F=-0.440, F=-0.267; P〈0.05）, while the correlation between Ang-2 mRNA and its protein, Ang-2/Ang-1 protein ratio and MVD was positive （F=0.319, F=-729, F=739; P〈0.05）. Moreover, MVD in groups with Ang-2 mRNAT/N ratio over 1.2 （the ratio of Ang-2 mRNA in stomach carcinoma to its adjacent normal mucosa） was higher than those with the ratio under 1.2. Conclusion： It was suggested that Ang-1 and Ang-2 antagonizes in the angiogenesis and the anglogenesis in tumor ultimately depended on Ang-2/Ang-1 ratio, once the expression of Ang-2 is higher than Ang-1 in some degree, the angiogenesis in tumors was promoted, otherwise oppositely. In other words, Ang-2 plays dominant role in the action of angiogenesis in tumors.展开更多
Hereditary angioedema(HAE)is an uncommon genetic disorder characterized by recurrent episodes of edema involving subcutaneous tissue and submucosa.The pathogenesis of HAE reflects an intricate coordinated regulation o...Hereditary angioedema(HAE)is an uncommon genetic disorder characterized by recurrent episodes of edema involving subcutaneous tissue and submucosa.The pathogenesis of HAE reflects an intricate coordinated regulation of components of complement,kinin and hemostatic pathway.Till date,mutations in 4 different genes have been identified to cause HAE which includes serine protease inhibitor G1(SERPING1),factor XII(F12),plasminogen(PLG)and angiopoietin 1(ANGPT 1).These mutations lead to increased bradykinin 2 receptor mediated signalling via increased production of bradykinin except mutations in ANGPT1 gene that disturbs the cytoskeletal assembly of vascular endothelial cells.In this review we aim to summarize the recent advances in the pathogenesis and genetics of HAE.We also provide an overview of possible future prospects in the identification of new genetic defects in HAE.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
基金Supported by a grant from the Natural Sciences Foundation of Fujian (No. C0110013).
文摘Objective： To explore angiopoietins （Ang-1, Ang-2）/Tie-2 expression and angiogenesis in stomach carcinomas. Methods： RT-PCR and immunohistochemistry were used to detect angiopoietins/Tie- 2 mRNA and protein expression in stomach carcinomas and their adjacent normal mucosa. Microvessel density （MVD） was counted according to CD34 immunohistochemical staining. Results： There was positive expression of Angiopoietins/Tie-2 mRNA and protein in stomach carcinomas and their paired adjacent normal mucosa. It was found that correlation between Ang-1 protein, Tie-2 mRNA expression and MVD was negative （F=-0.440, F=-0.267; P〈0.05）, while the correlation between Ang-2 mRNA and its protein, Ang-2/Ang-1 protein ratio and MVD was positive （F=0.319, F=-729, F=739; P〈0.05）. Moreover, MVD in groups with Ang-2 mRNAT/N ratio over 1.2 （the ratio of Ang-2 mRNA in stomach carcinoma to its adjacent normal mucosa） was higher than those with the ratio under 1.2. Conclusion： It was suggested that Ang-1 and Ang-2 antagonizes in the angiogenesis and the anglogenesis in tumor ultimately depended on Ang-2/Ang-1 ratio, once the expression of Ang-2 is higher than Ang-1 in some degree, the angiogenesis in tumors was promoted, otherwise oppositely. In other words, Ang-2 plays dominant role in the action of angiogenesis in tumors.
文摘形成血管和淋巴管内层的内皮细胞是脉管系统的重要组成部分,并参与血管和淋巴系统疾病的发病机制。内皮细胞上的血管生成素(Angiopoietin,Ang)-具有免疫球蛋白和表皮生长因子同源性结构域的酪氨酸蛋白激酶(Tyrosine kinase receptors with immunoglobulin and EGF homology domains,Tie)轴是除了血管内皮生长因子受体途径外胚胎心血管和淋巴发育所必需的第二种内皮细胞特异性配体-受体信号传导系统。Ang-Tie轴参与调节产后血管生成与重塑、血管通透性和炎症,以维持血管平衡,因此,该系统在许多血管和淋巴系统疾病中发挥重要的作用。针对近年来Ang-Tie轴在血管和淋巴系统相关疾病中作用的研究进展,文中系统论述了Ang-Tie轴在炎症诱导的血管通透性、血管重塑、眼部新生脉管、剪切应力反应、动脉粥样硬化和肿瘤血管生成和转移中的作用,并总结了涉及Ang-Tie轴的相关治疗性抗体、重组蛋白和小分子药物。
文摘Hereditary angioedema(HAE)is an uncommon genetic disorder characterized by recurrent episodes of edema involving subcutaneous tissue and submucosa.The pathogenesis of HAE reflects an intricate coordinated regulation of components of complement,kinin and hemostatic pathway.Till date,mutations in 4 different genes have been identified to cause HAE which includes serine protease inhibitor G1(SERPING1),factor XII(F12),plasminogen(PLG)and angiopoietin 1(ANGPT 1).These mutations lead to increased bradykinin 2 receptor mediated signalling via increased production of bradykinin except mutations in ANGPT1 gene that disturbs the cytoskeletal assembly of vascular endothelial cells.In this review we aim to summarize the recent advances in the pathogenesis and genetics of HAE.We also provide an overview of possible future prospects in the identification of new genetic defects in HAE.
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.
