Correlation of serum angiopoietin-1， angiopoietin-2， and angiopoietin-1/angiopoietin-2 ratio with HBV DNA and alanine aminotransferase in patients with chronic hepatitis B or liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the correlation of serum angiopoietin-1 （Ang-1）， angiopoietin-2 （Ang-2）， and Ang-1/Ang-2 ratio with HBA DNA and alanine aminotransferase （ALT） in patients with chronic hepatitis B （CHB） or liver cirrhosis. MethodsClinical data and serum specimens were collected from 99 patients with CHB and 59 patients with liver cirrhosis who were admitted to Beijing YouAn Hospital， Capital Medical University， from March 2018 to October 2019， and 46 individuals who underwent physical examination were enrolled as control group. PCR was used to measure serum HBV DNA level， and ELISA was used to measure the serum levels of Ang-1 and Ang-2. The serum levels of Ang-1 and Ang-2 and Ang-1/Ang-2 ratio were compared between groups. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Bonferroni method was used for further comparison between two groups； the Spearman correlation analysis was used to investigate the correlation of Ang-1， Ang-2， and Ang-1/Ang-2 ratio with HBV DNA and ALT. ResultsCompared with the control group， the CHB group and the liver cirrhosis group had a significant reduction in the level of Ang-1 （479.0 pg/mL and 208.4 pg/mL vs 671.0 pg/mL， both P<0.05）， and compared with the CHB group， the liver cirrhosis group had a significant reduction in the level of Ang-1 （P<0.001）. Compared with the control group， the CHB group and the liver cirrhosis group had a significant increase in the level of Ang-2 （286.1 pg/mL and 438.4 pg/mL vs 198.0 pg/mL， both P<0.001）， and compared with the CHB group， the liver cirrhosis group had a significant increase in the level of Ang-2 （P<0.001）. Compared with the control group， the CHB group and the liver cirrhosis group had a significant reduction in Ang-1/Ang-2 ratio （1.6 and 0.5 vs 3.4， both P<0.001）， and compared with the CHB group， the liver cirrhosis group had a significant reduction in Ang-1/Ang-2 ratio （P<0.001）. The Spearman correlation analysis showed that in the CHB group， Ang-1 was negatively correlated with HBV DNA and ALT （r=-0.400 and -0.394， both P˂0.001）， Ang-2 was positively correlated with HBV DNA and ALT （r=0.365 and 0.351， both P<0.001）， and Ang-1/Ang-2 ratio was negatively correlated with HBV DNA and ALT （r=-0.463 and -0.473， both P<0.001）； in the liver cirrhosis group， Ang-1， Ang-2， and Ang-1/Ang-2 ratio had no correlation with HBV DNA or ALT （all P>0.05）. ConclusionThere are significant changes in the serum levels of Ang-1 and Ang-2 and Ang-1/Ang-2 ratio in patients with CHB or liver cirrhosis， and Ang-1， Ang-2， and Ang-1/Ang-2 ratio reflects the degree of liver injury in patients with CHB to a certain extent.

Reduced Angiopoietin Factor 2 Levels Are Correlated with Better Cardiac Function and Prognosis in Valvular Heart Disease

ABSTRACT Introduction: There are few circulating biomarkers for valvular heart disease. Angiopoietin (Ang) 1, Ang2, and vascular endothelial growth factor are important inflammation-associated cytokines. The aim of this study was to investigate the clinical significance and association of Ang1, Ang2, and vascular endothelial growth factor in valvular heart disease. Methods: This is a retrospective study; a total of 62 individuals (valvular heart disease patients [n=42] and healthy controls [n=20]) were included. Plasma levels of Ang1, Ang2, and vascular endothelial growth factor were detected by enzyme-linked immunosorbent assays. We retrospectively collected the baseline characteristics and short-term outcomes; logistic regression was performed to identify predictor for short-term mortality. Results: Ang2 was significantly decreased in the valvular heart disease group compared with the healthy control group (P=0.023), while no significant difference was observed in the Ang1 and vascular endothelial growth factor levels. The Ang2 level of New York Heart Association (NYHA) I/II patients — but not NYHA III/IV patients — was significantly decreased compared with that of healthy control individuals (NYHA I/II: P=0.017; NYHA III/IV: P=0.485). Univariable logistic regression analysis indicated that Ang2 was a significant independent predictor for short-term mortality (odds ratio 18.75, P=0.033, 95% confidence interval 8.08-102.33). Ang1 was negatively correlated with Ang2 (P=0.032, Pearson's correlation coefficient =-0.317) and was positively correlated with vascular endothelial growth factor (P=0.019, Pearson's correlation coefficient = 0.359). Conclusion: Ang2 might serve as a therapeutic and prognostic target for valvular heart disease.

Correlation analysis of serum KLF2,Ang1 levels with severity and prognosis of neonatal respiratory distress syndrome / 国际检验医学杂志

Objective To investigate the correlation of serum levels of Krüppel-like transcription factor 2(KLF2)and angiopoietin-1(Ang1)with the severity and prognosis of neonatal respiratory distress syndrome(NRDS).Methods A total of 416 children with NRDS who were treated in this hospital from January 2019 to December 2022 were selected as the NRDS group.According to the results of chest imaging examination,the NRDS group was divided into mild group(145 cases),moderate group(174 cases)and severe group(97 ca-ses).According to NRDS outcome the children were divided into the good prognosis group 322 cases and bad prognosis group 94 cases,another 150 healthy premature infants were selected as the control group in the hos-pital.Serum KLF2,Ang1 levels were measured by enzyme-linked immunosorbent assay(ELISA).Pearson correlation was used to analyze the correlation between serum KLF2,Ang1 levels and neonatal acute physiolo-gy score perinatal supplement Ⅱ(SNAPPE-Ⅱ),1 min Apgar score in neonates with NRDS.The receiver op-erating characteristic(ROC)curve was used to evaluate the value of serum KLF2,Ang1 levels in predicting the prognosis of children with NRDS.Results Compared with the control group,the NRDS group had signifi-cantly lower birth weight and serum KLF2,Ang1 levels(P<0.05).In the children with NRDS,the serum of KLF2,Ang1 levels and 1 min Apgar score gradually decreased with the increase in the severity of the disease(P<0.05).Compared with the good prognosis group,the children with NRDS in the poor prognosis group had significant decreased in the serum KLF2 and Ang1 levels and a significant increased in the SNAPPE-Ⅱscore(P<0.05).In children with NRDS,the serum levels of KLF2 and Ang1 were negatively correlated with SNAPPE-Ⅱ score and positively correlated with 1 min Apgar score(P<0.05).The area under the curve(AUC)of serum KLF2 and Ang1 levels in predicting the poor prognosis of NRDS children were 0.931 and 0.909,respectively.The AUC of the combination of KLF2 and Ang1 in predicting the poor prognosis of NRDS children was 0.949,which was higher than that of KLF2 or Ang1 alone,with a sensitivity of 96.81%.Conclu-sion Serum KLF2,Ang1 levels in children with NRDS are reduced,the two level with NRDS children with severe degree aggravating gradually decreas,and both have important value in predicting the prognosis of chil-dren with NRDS.

The relationship between angiopoietin 1 and Smadhomolog 9 gene expression in cancer tissues and tumor metastasis, invasion behavior and prognosis in patients with lung adenocarcinoma / 中国医师进修杂志

Objective:To explore the relationship between the expression of angiopoietin 1 (ANGPT1) and Smadhomolog 9 (Smad9) genes in cancer tissues and tumor metastasis, invasion behavior and prognosis in patients with lung adenocarcinoma.Methods:Sixty patients with lung adenocarcinoma in Chengwu Hospital Affiliated to Shandong First Medical University from October 2018 to December 2019 were selected as the research objects. The expressions of ANGPT1 and Smad9 mRNA in cancer tissues and adjacent tissues were compared, as well as the expressions of ANGPT1 and Smad9 mRNA in cancer tissues of patients with different tumor metastasis and invasion behaviors. The relationship between ANGPT1 and Smad9 mRNA expression and tumor metastasis and invasion behavior of lung adenocarcinoma were analyzed, and the 1-year survival rate of patients with lung adenocarcinoma was calculated. The 1-year survival rate of patients with different ANGPT1 and SMAD9 mRNA expression levels were compared.Results:The relative expression of ANGPT1 mRNA and Smad9 mRNA in cancer tissues were lower than those in adjacent tissues: 2.45 ± 0.26 vs. 11.18 ± 0.93, 4.23 ± 0.31 vs. 7.58 ± 0.65, the differences were statistically significant ( P<0.05). There were significant differences in the relative gene expression of ANGPT1 and Smad9 mRNA in different clinical stages, tumor diameter, degree of differentiation, lymph node metastasis and pleural invasion ( P<0.05). Spearman correlation analysis showed that the expression of ANGPT1 and Smad9 mRNA were negatively correlated with clinical stage, tumor diameter, lymph node metastasis and pleural invasion ( r = - 0.517, - 0.539, - 0.606, - 0.679, P<0.05), and positively correlated with the degree of differentiation ( r = 0.628, P<0.05). The 1-year survival rate of 58 patients was 72.41%. Kaplan-Meier curve analysis showed that the 1-year survival rate of patients with low expression of ANGPT1 and Smad9 mRNA in cancer tissues were were lower than those in patients with high expression ( P<0.05). Conclusions:Down-regulation of ANGPT1 and Smad9 genes in cancer tissues will accelerate the metastasis and invasion behavior of lung adenocarcinoma. Up-regulating the expression of both genes can be a potential way to improve survival.

Relationship between the expression and ratio of Ang-1 and Ang-2 in serum and prognosis in patients with cervical cancer / 中国医师杂志

Objective:To investigate the expression and ratio of serum angiopoietin-1/-2 (sAng-1/-2) in patients with cervical cancer and its relationship with clinicopathological features and prognosis.Methods:Eighty-seven patients with cervical cancer (FIGO Ⅰa1-Ⅳ) who were admitted to the First Affiliated Hospital of Shihezi University School of Medicine from September 2015 to December 2017 were selected as subjects. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of sAng-1 and sAng-2 in serum samples of 87 patients at admission. The correlation between the sAng-1 and sAng-2 levels was analyzed by statistical analysis.Results:The expression of sAng-1 in patients with Ⅰa1-Ⅱa2 was significantly higher than those in advanced stage of Ⅱb-Ⅳ ( P<0.05). The expression of sAng-2 in patients with Ⅱb-Ⅳ or adenocarcinoma was significantly higher than that of patients with Ⅰa1-Ⅱa2 or squamous cell carcinoma ( P<0.05). The ratio of sAng-2/sAng-1 in patients with lymph node metastasis or Ⅱb-Ⅳ stage was higher than that in patients without lymph node metastasis or Ⅰa1-Ⅱa2 ( P<0.05). In addition, the expression level of sAng-2 and sAng-2/sAng-1 ratio in cervical cancer patients were related to the 3-year overall survival (OS) and pregression-free survival (PFS) ( P<0.05). Conclusions:The expression of sAng-1 and sAng-2 in patients with cervical cancer may be related to tumor pathological type, disease progression or prognosis. The expression of sAng-2 or the ratio of sAng-2/sAng-1 may be tumor markers to evaluate the prognosis of patients with cervical cancer.

Advances of Angiopoietin-Tie axis in vascular and lymphatic system-related diseases / 生物工程学报

Endothelial cells that form the inner layers of both blood and lymphatic vessels are important components of the vascular system and are involved in the pathogenesis of vascular and lymphatic diseases. Angiopoietin (Ang)-Tie axis in endothelial cells is the second endothelium-specific ligand-receptor signaling system necessary for embryonic cardiovascular and lymphatic development in addition to the vascular endothelial growth factor receptor pathway. The Ang-Tie axis also maintains vascular homeostasis by regulating postnatal angiogenesis, vessel remodeling, vascular permeability, and inflammation. Therefore, the dysfunction of this system leads to many vascular and lymphatic diseases. In light of the recent advances on the role of the Ang-Tie axis in vascular and lymphatic system-related diseases, this review summarizes the functions of the Ang-Tie axis in inflammation-induced vascular permeability, vascular remodeling, ocular angiogenesis, shear stress response, atherosclerosis, tumor angiogenesis, and metastasis. Moreover, this review summarizes the relevant therapeutic antibodies, recombinant proteins, and small molecular drugs associated with the Ang-Tie axis.

Effect of Exercise Type on Vascular Stabilization Factor in Ischemic Stroke Patients.

Stroke is one of the leading causes of mortality and disability in the world. The angiogenesis strategy is a new therapeutic approach to exercise in these patients. The purpose of this study was to investigate the effect of continuous exercise on serum levels of vascular stabilizing factor and its consequences. MethodsIn this randomized clinical trial study, 30 patients with stroke who volunteered to participate in the study, aged 45 - 65 years, were selected by convenience sampling and non-random sampling method. Subjects were randomly selected. The patients were randomly divided into intervention group (4 weeks of continuous exercise in 40 - 60 minutes pedal with 60 - 65% VO2 peak intensity for 5 days per week and physiotherapy) and control group (physiotherapy only). Blood angiogenesis and motor function levels were measured at baseline and twenty-eight days after the last exercise session. Data was analyzed by using Stata software version 13 at the significance level of 0.05. ResultsIn this trial, thirty patients completed the study period, and were included in the analysis. The mean ages of patients in the control and intervention groups were 55.66 (S.D.: 6.69) and 61.46 (S.D.: 6.47) years, respectively. Serum levels of angiopoietin-1 increased after exercise at alpha level (P = 0.011). The reduction of the Modified Rankin Scale was obtained as a secondary consequence (P = 0.001). ConclusionsContinuous exercise training over four weeks can improve the prognosis of patients by altering the levels of angiogenesis-stabilizing factor in decreasing the symptoms of stroke.

Expression of angiopoietin-1 during scar strophying / 中华医学美学美容杂志

Objective To explore the expression of angiopoietin 1 in scar during the scar strophying.Methods The rabbit ear scar model was established in the same position of each ear ventral center skin regardless of gender.The weight of each rabbit was greater than 2.0 kg weight.The scars were collected at weeks 1,2,4,8,and 12.After 12 weeks of scar tissue samples were collected,together with normal skin tissues in the rabbit ear ventral normal skin.The tissues were preseved in 10％ formalin liquid and cryopreserved in liquid nitrogen,respectively.The general form of scar tissues and the expression of Ang-1 in scar were investigated by hematoxylin and eosin staining and Western-blot.Results The expression of Ang-1 increased gradually,and the highest at 2 week after epithelial change as (0.29±0.11),then decreased gradually,and the lowset at week 12 as (0.00± 0.00),which was close to normal skin expression as (0.05±0.01) (P＜0.05).Conclusions Ang-1 may play an important role during the scar atrophying.

Study of angiopoietin and plasminogen genes in hereditary angioedema

SUMMARY OBJECTIVE To investigate the presence of the Angiopoietin 1 (ANGPT1) and Plasminogen (PLG) mutations in patients with Hereditary Angioedema (HAE) and normal C1 esterase inhibitor (C1-INH) levels, who do not harbor the F12 gene mutation. METHODS Patients clinically diagnosed with HAE but without C1-INH deficiency or dysfunction and F12 gene mutation were evaluated. DNA extraction, quantification, and dilution were performed at a concentration of 100 ng/µL, followed by a DNA amplification (PCR) for molecular evaluation of exon 2 of the ANGPT1 gene and exon 9 of the PLG gene for identification of mutations c.807G>T / p.A119S and c.988A>G / p.K330E, respectively. The PCR product was evaluated in 1% agarose gel electrophoresis. Sequencing was performed using the Sanger method. The electropherograms were analyzed using the FASTA® program. RESULTS DNA samples from 15 women were sequenced. Their ages ranged from 10 to 60 years and the normal C1 esterase and C4 inhibitor serum levels ranged from 22 to 39 mg/dL and from 10 to 40 mg/dL, respectively. No mutations were detected in the analyzed exons of ANGPT1 and PLG. However, a single-nucleotide polymorphism (SNP) was detected in two homozygotic and five heterozygotic patients. CONCLUSION Further studies are needed to evaluate these SNPs and scrutinize their potential for use as molecular markers of HAE and as novel therapeutic targets.

RESUMO OBJETIVO Investigar a presença das mutações no gene Angiopoietina (ANGPT1) e gene Plasminogênio (PLG) em pacientes com Angioedema Hereditário (AEH) com inibidor C1 esterase (C1-INH) normal e negativos para mutação do gene F12. MÉTODOS Foram avaliados pacientes com diagnóstico clínico de AEH sem deficiência ou disfunção de C1-INH e negativos para mutação do gene F12. Realizou-se extração, quantificação e diluição do DNA a uma concentração de 100 ng/uL, em seguida amplificação do DNA (PCR) para avaliação molecular do exon 2 do gene ANGPT1 e do exon 9 do gene PLG para identificação das mutações c.807G>T.p.A119S e c.988A>G p.K330E, respectivamente. O produto da PCR foi avaliado em eletroforese em gel de agarose 1%. Foi realizado o sequenciamento pelo método de Sanger. As análises dos eletroferogramas foram realizadas pelo programa FASTA®. RESULTADOS Foram sequenciadas amostras de 15 mulheres, idade entre 10 e 60 anos, com níveis séricos de inibidor de C1 esterase e C4 normais variando de 22 a 39mg/dL e 10 a 40mg/dL, respectivamente. Não foram identificadas mutações nos éxons analisados dos genes ANGPT1 e PLG. Entretanto no gene PLG foram encontrados polimorfismo de nucleotídeo único (SNP), em duas pacientes homozigotas e cinco heterozigotas. CONCLUSÃO Mais estudos sobre SNP são necessários para esclarecer estes achados pois eles podem ser utilizados como marcadores moleculares do AEH e alvo para novos tratamentos.

Combination of stromal vascular fraction and Ad-COMP-Ang1 gene therapy improves long-term therapeutic efficacy for diabetes-induced erectile dysfunction / 亚洲男科学杂志(英文版)

Men with diabetic erectile dysfunction (ED) respond poorly to the currently available oral phosphodiesterase-5 inhibitors. Therefore, functional therapies for diabetic ED are needed. Stromal vascular fraction (SVF) and the adenovirus-mediated cartilage oligomeric matrix angiopoietin-1 (Ad-COMP-Ang1) gene are known to play critical roles in penile erection. We previously reported that SVF and Ad-COMP-Ang1 have only a short-term effect in restoring erectile function. Further improvements to ED therapy are needed for long-lasting effects. In the present study, we aimed to test if the combination of SVF and Ad-COMP-Ang1 could extend the erection effect in diabetic ED. We found that the combination therapy showed a long-term effect in restoring erectile function through enhanced penile endothelial and neural cell regeneration. Combination therapy with SVF and Ad-COMP-Ang1 notably restored cavernous endothelial cell numbers, pericyte numbers, endothelial cell-cell junctions, decreased cavernous endothelial cell permeability, and promoted neural regeneration for at least 4 weeks in diabetic mice. In summary, this is an initial description of the long-term effect of combination therapy with SVF and Ad-COMP-Ang1 in restoring erectile function through a dual effect on endothelial and neural cell regeneration. Such combination therapy may have therapeutic potential for the treatment of diabetic ED.

Relation of angiopoietin-1 with prognoses of patients with acute ischemic stroke / 中华神经医学杂志

Objective To investigate the relation of angiopoietin-1 (Ang-1) with prognoses of patients with acute ischemic stroke.Methods Eighty-nine patients with acute ischemic stroke,admitted to our hospitals fiom October 2015 to December 2017,were chosen.The patients were diagnosed as having acute ischemic stroke by digital subtraction angiography (DSA),and assessed with National Institute of Health Stroke Scale (NIHSS) on the time of admission and 21st d of admission;modified Rankin Scale (mRS) was performed on 90th d of admission.According to NIHSS and mRS scores,these patients were divided into a good prognosis group (difference value of NIHSS scores＞0,mRS scores≤ 2) and a poor prognosis group (difference value ofNIHSS scores≤ 0,mRS scores＞2).In addition,31 patients without acute ischemic stroke who were randomly selected as a control group at the same time.The clinical data of all study subjects were collected.Morning fasting blood of the patients was collected on 2nd,7th,14th,and 21st d of admission.The serum Ang-1 expression was detected by ELISA.Results (1) Fifty-seven patients were into the good prognosis group and 32 were into the poor prognosis group;there were no significant differences in age,gender,hypertension history,diabetes history,smoking history,and drinking history among the control group,good prognosis group and poor prognosis group (P＞0.05).(2) There was no statistically significant difference in Ang-1 expression level in control group among different time points (P＞0.05);however,Ang-1 level in the good prognosis group and the poor prognosis group was the highest on 2n d of admission,and then,gradually decreased,and it still had high expression on the 21st d;significant differences were noted among the 3 groups on 2nd,7th,14th,and 21st d of admission (P＜0.05),and Ang-1 level in the good prognosis group was significantly higher than that in the poor prognosis group and control group (P＜0.05).Conclusion Ang-1 level increases in patients with acute ischemic stroke;Ang-1 level in good prognosis patients is higher than that in poor prognosis patients,suggesting that Ang-1 may be related to their prognoses.

Combination of stromal vascular fraction and Ad-COMP-Ang1 gene therapy improves long-term therapeutic efficacy for diabetes-induced erectile dysfunction / 亚洲男科学杂志(英文版)

Men with diabetic erectile dysfunction (ED) respond poorly to the currently available oral phosphodiesterase-5 inhibitors. Therefore, functional therapies for diabetic ED are needed. Stromal vascular fraction (SVF) and the adenovirus-mediated cartilage oligomeric matrix angiopoietin-1 (Ad-COMP-Ang1) gene are known to play critical roles in penile erection. We previously reported that SVF and Ad-COMP-Ang1 have only a short-term effect in restoring erectile function. Further improvements to ED therapy are needed for long-lasting effects. In the present study, we aimed to test if the combination of SVF and Ad-COMP-Ang1 could extend the erection effect in diabetic ED. We found that the combination therapy showed a long-term effect in restoring erectile function through enhanced penile endothelial and neural cell regeneration. Combination therapy with SVF and Ad-COMP-Ang1 notably restored cavernous endothelial cell numbers, pericyte numbers, endothelial cell-cell junctions, decreased cavernous endothelial cell permeability, and promoted neural regeneration for at least 4 weeks in diabetic mice. In summary, this is an initial description of the long-term effect of combination therapy with SVF and Ad-COMP-Ang1 in restoring erectile function through a dual effect on endothelial and neural cell regeneration. Such combination therapy may have therapeutic potential for the treatment of diabetic ED.

Influence of adenosine preconditioning on vascular endothelial growth factor and angiopoietin-1 in oxygen-glucose deprivation and reoxygenation astrocytes / 新乡医学院学报

Objective To explore the effect of adenosine preconditioning on vascular endothelial growth factor(VEGF)and angiopoietin-1 (Ang-1) in oxygen-glucose deprivation and reoxygenation astrocytes.Methods Astrocytes of pallium in Sprague Dawley rats were cultured in vitro,and the third generation of astrocytes were passaged to 96 pore plate.The astrocytes were divided into normal control group,oxygen-glucose deprivation group and adenosine preconditioning group randomly when the astrocytes adhered to the wall and grew the evection.The cells in the normal control group did not received oxygen glucose deprivation;the cells in the oxygen-glucose deprivation group received oxygen-glucose deprivation 8 h and reoxygenation 24 h;the cells in the adenosine preconditioning group were given adenosine 100 μmol · L-1 at 24 hours before received oxygen-glucose deprivation 8 h and reoxygenation 24 h.The shape of astrocytes were observed after reoxygenation 24 h.The cytoactivity of astrocytes in each group was detected by methyl thiazolyl tetrazolium assay;the concentration of VEGF and Ang-1 in supernatant of astrocytes in each group was detected by enzyme linked immunosorbent assay.Results The astrocytes in the normal control group grew well.The edema of astrocytes in the oxygen-glucose deprivation group was obvious,and the cell body became round;the cell morphology changed from irregular to spindle shape;and the neurites became shorter or even disappeared.Compared with the oxygen-glucose deprivation group,the astrocytes in the adenosine preconditioning group had a mildly edema,and the cells were arranged orderly.The vitality of astrocytes in the normal control group,oxygen-glucose deprivation group and adenosine preconditioning group was 0.698 ± 0.059,0.196 ± 0.062,0.412 ± 0.009 respectively;the vitality of astrocytes in the oxygen-glucose deprivation group was obviously lower than that in the normal control group(q =3.561,P ＜0.05);the vitality of astrocytes in the adenosine preconditioning group was obviously higher than that in the oxygen-glucose deprivation group (q =2.102,P ＜ 0.05).The concentration of VEGF in supemate in the normal control group,oxygen-glucose deprivation group and adenosine preconditioning group was (0.038 ± 0.005),(0.053 ± 0.007),(0.084 ± 0.006) μg · L-1 respectively;the concentration of Ang-1 in supemate in the normal control group,oxygen-glucose deprivation group and adenosine preconditioning group was (0.030 ± 0.007),(0.049 ± 0.008),(0.080 ± 0.004) μg · L-1 respectively.The concentration of VEGF and Ang-1 in the oxygen-glucose deprivation group were obviously higher than those in the normal control group(q =1.394,1.633;P ＜ 0.05);the concentration of VEGF and Ang-1 in the adenosine preconditioning group were obviously higher than those in the oxygen-glucose deprivation group (q =1.584,1.632;P ＜ 0.05).Conclusion The adenosine preconditioning can increase the expression of VEGF and Ang-1 in astrocytes after oxygen-glucose deprivation.It can enhance the tolerance of brain to ischemia-reperfusion injury and produce neural protection effect.

Angiopoietin-1 and -2 and vascular endothelial growth factor expression in ovarian grafts after cryopreservation using two methods / 대한생식의학회지

OBJECTIVE: The favored method of preserving fertility in young female cancer survivors is cryopreservation and autotransplantation of ovarian tissue. Reducing hypoxia until angiogenesis takes place is essential for the survival of transplanted ovarian tissue. The aim of this study was to investigate the role of angiopoietin-1 (Angpt-1), angiopoietin-2 (Angpt-2), and vascular endothelial growth factor (VEGF) in ovarian tissue grafts that were cryopreserved using two methods. METHODS: Ovarian tissues harvested from ICR mice were divided into three groups: group I (control), no cryopreservation; group II, vitrification in EFS (ethylene-glycol, ficoll, and sucrose solution)-40; and group III, slow freezing in dimethyl sulfoxide. We extracted mRNA for VEGF, Angpt-1, and Angpt-2 from ovarian tissue 1 week following cryopreservation and again 2 weeks after autotransplantation. We used reverse transcriptase-polymerase chain reaction to quantify the levels of VEGF, Angpt-1, and Angpt-2 in the tissue. RESULTS: Angpt-1 and Angpt-2 expression decreased after cryopreservation in groups II and III. After autotransplantation, Angpt-1 and Angpt-2 expression in ovarian tissue showed different trends. Angpt-1 expression in groups II and III was lower than in group I, but Angpt-2 in groups II and III showed no significant difference from group I. The vitrified ovarian tissues had higher expression of VEGF and Angpt-2 than the slowfrozen ovarian tissues, but the difference was not statistically significant. CONCLUSION: Our results indicate that Angpt-2 may play an important role in ovarian tissue transplantation after cryopreservation although further studies are needed to understand its exact function.

Clinicopathological significance and biological behavior of ANGPTL1 expression in human colorectal cancer / 中华普通外科杂志

Objective To study the clinicopathological significance and biological behavior of human colorectal cancer (CRC) with the expression of angiopoietin-like protein 1 (ANGPTL1).Methods The expression of ANGPTL1 protein in 98 paraffin embedded CRC specimens and paired adjacent non cancerous tissues were detected by immunohistochemistry.The relationship between the protein expression and clinicopathological features was analyzed.Western blot and qRT-PCR were used to examine the expression of ANGPTL1 protein and mRNA levels in 24 paired fresh CRC and adjuvant non-cancerous tissues.Finally,ANGPTL1 expression in CRC cell lines with different metastatic capabilities was detected by WB.Cell invasion and migration were detected using ANGPTL1 siRNA.Results ANGPTL1 expression in CRC tissues was much lower than that in non-cancerous tissues (44％ vs.76％,P ＜ 0.01).ANGPTL1 expression was negatively associated with T stage (x2 =5.766,P =0.016),lymph node metastasis (x2 =5.571,P =0.018) and TNM stage (x2 =7.773,P =0.005).Moreover,CRC patients with ANGPTL1 positive expression had a better prognosis.ANGPTL1 protein and mRNA levels in CRC tissues were higher than in non-cancerous tissues (t =3.126,P =0.005;t =2.523,P =0.019).ANGPTL1 interference promoted cell invasion and migration of HCT116 cells.Conclusion ANGPTL1 expression is closely associated with tumor T stage,lymph node metastasis,TNM stage and worse prognosis of CRC patients.ANGPTL1 inhibits cell invasion and migration of CRC cells.

Angiopoietin-1 Modified Human Umbilical Cord Mesenchymal Stem Cell Therapy for Endotoxin-Induced Acute Lung Injury in Rats

PURPOSE: Angiopoietin-1 (Ang1) is a critical factor for vascular stabilization and endothelial survival via inhibition of endothelial permeability and leukocyte- endothelium interactions. Hence, we hypothesized that treatment with umbilical cord mesenchymal stem cells (UCMSCs) carrying the Ang1 gene (UCMSCs-Ang1) might be a potential approach for acute lung injury (ALI) induced by lipopolysaccharide (LPS). MATERIALS AND METHODS: UCMSCs with or without transfection with the human Ang1 gene were delivered intravenously into rats one hour after intra-abdominal instillation of LPS to induce ALI. After the rats were sacrificed at 6 hours, 24 hours, 48 hours, 8 days, and 15 days post-injection of LPS, the serum, the lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested for analysis, respectively. RESULTS: Administration of fluorescence microscope confirmed the increased presence of UCMSCs in the injured lungs. The evaluation of UCMSCs and UCMSCs-Ang1 actions revealed that Ang1 overexpression further decreased the levels of the pro-inflammatory cytokines TNF-α, TGF-β1, and IL-6 and increased the expression of the anti-inflammatory cytokine IL-10 in the injured lungs. This synergy caused a substantial decrease in lung airspace inflammation and vascular leakage, characterized by significant reductions in wet/dry ratio, differential neutrophil counts, myeloperoxidase activity, and BALF. The rats treated by UCMSCs-Ang1 showed improved survival and lower ALI scores. CONCLUSION: UCMSCs-Ang1 could improve both systemic inflammation and alveolar permeability in ALI. UC-derived MSCs-based Ang1 gene therapy may be developed as a potential novel strategy for the treatment of ALI.

Effect of up-regulation of miR-132 on expressions of angiopoietin-1/endothelium-specific tyrosine kinase receptor 2 in focal cerebral ischemia reperfusion injury of rats / 中华神经医学杂志

Objective To investigate the effect of up-regulation of miR-132 on expressions of angiopoietin-1 (Ang-1)/endothelium-specific tyrosine kinase receptor 2 (Tie2) in focal cerebral ischemia reperfusion injury of rats.Methods Forty adult healthy SD rats were randomly divided into sham-operated group,cerebral ischemia group,miR-132 mimic group and negative control group (n=10).The models of middle cerebral artery occlusion in the later three groups were established by using modified Longa suture method.Rats in the miR-132 mimic group and negative control group were injected miR-132 mimic 15 μg and negative control 15 μg via paracele.Rats in each group were sacrificed 24 h after ischemia,and the brain tissues were collected;the total infarct volumes were calculated by TTC staining.The mRNA expressions ofmiR-132,Ang-1 and Tie2 in ischemic cerebral cortex tissues were detected by real-time fluorescence quantitative PCR.The protein expressions of Ang-1,Tie2,CD31 and vessel endothelial growth factor (VEGF) in ischemic cerebral cortex tissues were detected by Western blotting.Results The total infarct volume in the miR-132 mimic group was (27.92±3.05) mm3,which was significantly smaller than that in the cerebral ischemia group and negative control group ([51.34±2.86] mm3 and [50.46±2.57] mm3,P＜0.05).The relative mRNA expression levels of miR-132,A ng-1,Tie2,and the protein expression levels of Ang-1,Tie2,CD31,VEGF in the ischemic cerebral cortex tissues of the miR-132 mimic group were significantly higher than those in the negative control group,cerebral ischemia group and sham-operated group (P＜0.05);and those in the negative control group and cerebral ischemia group were significantly higher than those in the sham-operated group (P＜0.05).Conclusion Up-regulation ofmiR-132 expression could improve the ischemic states of ischemic stroke in rats,which might be related to Ang-1/Tie2 increased expressions to promote angiogenesis in ischemic brain tissues.

Angiopoietin-1 and Angiopoietin-2 Expression Imbalance Influence in Early Period After Subarachnoid Hemorrhage / 대한배뇨장애요실금학회지

PURPOSE: Microvascular endothelial integrity is important for maintaining the blood-brain barrier (BBB). However, subarachnoid hemorrhage (SAH) disrupts this integrity, making the BBB dysfunctional—an important pathophysiological change after SAH. Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) regulate microvascular permeability by balancing each other’s expression. METHODS: This study investigated the dynamics of Ang-1 and Ang-2 expression after SAH and the protective effect of Ang-1 on BBB functioning using an endovascular puncture model of rat SAH. The Ang-1 and Ang-2 expression in brain tissue was determined by immunohistochemistry. In addition, Western blotting was used to estimate Ang-1 and Ang-2 concentration and to compare them at 6–72 hours post-SAH cortex and hippocampus. Evans blue viability assay was used to evaluate BBB permeability, and neurological testing was implemented to evaluate neurological impairment during SAH. RESULTS: It was found that following SAH, Ang-1 expression decreases and Ang-2 expression increases in the cortex, hippocampus, and microvessels. The Ang-1/Ang-2 ratio decreased as quickly as 6 hours after SAH and reached its lowest 1 day after SAH. Finally, it was found that exogenous Ang-1 reduces SAH-associated BBB leakage and improves neurological function in post-SAH rats. CONCLUSIONS: Our findings suggest that the equilibrium between Ang-1 and Ang-2 is broken in a period shortly after SAH, and the treatment of exogenous Ang-1 injection alleviates neurological dysfunctions through decreasing BBB destruction.

TIMP-1 and Ang-1 gene-modified BMSCs transplantation to improve cardiac function of rats with myocardial infarction / 中华器官移植杂志

Objective To evaluate the effects of TIMP-1 and Ang-1 gene-modified BMSCs transplantation on the left ventricular function of rats with myocardial infarction.Methods The rat BMSCs were.transfected with eukaryotic expression plasmid encoding TIMP-1 or/and Ang-1 gene by liposome.Acute myocardial infarction was made in male rats by ligation of the left anterior descending (LAD) coronary artery.BMSCs carrying TIMP-1 or/and Ang-1 gene were injected into the ischemic myocardium after LAD ligatior.Four weeks after the administration,cardiac function was assessed by echocardiography and the hearts were harvested and sectioned for immunohistochemistry to examine the apoptosis,the collagen content and angiogenesis density.Results TIMP-1 and Ang-1 genemodified BMSCs transplantation significantly improved the cardiac function,myocardial apoptosis was alleviated,collagen content decreased and the angiogenesis density in border-zone was increased significantly (P＜0.05).Conclusions The results suggest that the combination of TIMP-1 and Ang-1-gene modified BMSCs transplantation can improve the cardiac function of rats with myocardial infarction.The increase of the blood supply,the alleviation of myocardial apoptosis and ventricle remolding after myocardial infarction possibly play important roles in the mechanism.

Relationship between serum Angiopoietin-1 level and the onset, the severity and the prognosis at 90 d of acute cerebral infarction / 临床神经病学杂志

Objective To investigate the relationship between serum Angiopoietin-1 ( Ang-1 ) level and the onset, the severity and the prognosis at 90 d of acute cerebral infarction.Methods The level of serum Ang-1 was measured in 132 acute cerebral infarction patients ( case group ) and 108 healthy controls ( control group ) .The relevant clinical data was also collected.NIHSS was assessed at admission.The severity of the condition was defined according to the NIHSS score.NIHSS score <5, 5 -15 and ≥16 were defined as minor, moderate and severe condition, respectively.mRS was assessed at 90 d after admission.mRS≤2 was defined as good outcome and otherwise defined as poor outcome.Results Compared with control group, proportion of patients who had a history of smoking, hypertension, diabetes mellitus and atrial fibrillation were significant higher, serum Ang-1 concentration was significant lower ( all P<0.05 ) .Logistic analysis showed that serum Ang-1 level and a history of diabetes mellitus were associated with the occurrence of acute cerebral infarction ( all P<0.01 ) .The serum Ang-1 level in minor, moderate and severe condition patients was (1.12 ±0.35) ng/ml, (0.96 ±0.39) ng/ml and (0.76 ±0.49) ng/ml.There were significant differences among them ( P=0.003) .There was a significant relationship between the severity and the serum Ang-1 level ( r=-0.267, P=0.002 ) .Compared with good outcome patients, the poor outcome patients had significant higher NIHSS score and higher proportion of a history of hypertension, diabetes mellitus, atrial fibrillation, and lower serum Ang-1 concentration ( all P<0.05 ) .NIHSS score and serum Ang-1 concentration at admission had a significant relationship with 90 d outcome of acute cerebral infarction patients ( all P<0.01) .Conclusion Serum Ang-1 level was lower in acute cerebral infarction patients and it had significant relationship with the onset, severity and 90 d outcome of acute cerebral infaration.