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.

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.

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.

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.

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.

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.

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.

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.

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.

Expression and clinical significance of macrophage inflammatory protein -1α,interferon gamma inducible protein 10 and angiopoietin-1 in primary acute myelogenous leukemia / 中国基层医药

Objective To study the expression of macrophage inflammatory protein-1α(MIP-1α),inter-feron gamma inducible protein 10(IP -10)and angiopoietin -1 (Ang -1)in primary acute myelogenous leukemia (AML),and clarify their clinical significance.Methods ELISA was used to detect the expressions of MIP -1α,IP-10 and Ang -1 in serum samples from 54 AML patients(observation group),and twenty volunteers(normal control group).Results The expression levels of MIP -1α,IP -10 and Ang -1 in the observation group[(198.813 ± 53.923)pg/mL,(2.332 ±0.745)ng/mL,(1.593 ±0.447)ng/mL]were significantly higher than the normal control group[(153.309 ±44.475)pg/mL,(1.569 ±0.485)ng/mL,(0.838 ±0.333)ng/mL](t =3.369,5.133,6.856, all P 0.05).There were remarkable correlation between the serum expression levels of MIP -1αand Ang -1 (r =0.324,P <0.05).Conclusion There are differences of serum MIP -1α, IP -10 and Ang -1 in the different NCCN prognosis groups,which reflect they may have certain guiding significance in the choice of clinical treatment and the prognosis for newly diagnosed AML.

Measurement of serum levels of angiogenic factors and inflammatory cytokines in patients w ith moyamoya disease by cytometric bead array / 国际脑血管病杂志

Objective To detect the serum levels of angiogenic factors and inflammatory cytokines in patients w ith moyamoya disease and explore their roles in the pathogenesis of the disease. Methods The serum levels of vascular endothelial grow th factor (VEGF), angiopoietin -1 (Ang-1), interleukin-8 (IL-8), granulocyte colony stimulating factor (G -CSF), granulocyte-macrophage colony stimulating factor ( GM-CSF) and monocyte chemotactic protein 1 (MCP -1) in 56 patients w ith moyamoya disease and 26 healthy controls w ere measured by cytometric bead array. Results The serum levels of VEGF (2.81 ± 1.77 pg/ml vs.1.98 ±0.66 pg/ml; t = 3.081, P = 0.003 ) and IL-8 (0.89 ±0.69 pg/ml vs.0.63 ± 0.45 pg/ml; t'=2.0371, P < 0.05) in the moyamoya disease group w ere significantly higher than those in the healthy control group, and the serum level of Ang -1 in the moyamoya disease group w as significantly low er than that in the healthy control group (830.01 ±289.29 pg/ml vs.961.65 ±232.87 pg/ml; t =-2.032, P =0.045). Conclusions There are significant difference in serum levels of VEGF, Ang -1 and IL-8 betw een patients w ith moyamoya disease and healthy controls. The results indicate that angiogenic factors and inflammatory cytokines play some roles in the pathogenesis of moyamoya disease.

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.

Effects of dexamethasone pretreatment on expression of angiopoietin-1, 2 in rats with acute lung injury induced by phosgene / 中华急诊医学杂志

Objective To investigate the effect of dexamethasone on expressions of angiopoietin-1,2 (Ang-1,2) in rats with acute lung injury induced by phosgene.Methods A total of 36 SD rats were randomly (random number) divided into 3 groups:normal control group that consisted of the rats with air exposure,phosgene group that consisted of the rats with exposure to 8.33 mg/L phosgene (purity 100％,of the same volume as the inhaled air in the normal control group) for 5 minutes and dexamethasone group that consisted of the rats with caudal vein injection of 2.5 mg/kg dexamethasone an hour before exposure to the same dose of phosgene.Wet and dry ratio of the lung (W/D) was calculated,and leukocyte count and total protein content of bronchoalveolar lavage fluid (BALF) were recorded 2 hours later.The concentrations of Ang-1,2 in the serum and BALF were measured by enzyme-linked immunosorbent assay (ELISA).Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the mRNA levels of Ang-1,2 and Tie-2 in the lung tissue.The protein expression of Ang-1,2 and Tie-2 in the lung tissue were quantified by Western blot.Results Compared with phosgene group,the lung W/D,protein content of BALF and WBC count in dexamethasone group were significantly decreased (P ＜ 0.01).Compared with normal control group,Ang-1 and Tie-2 expressions in phosgene group were significantly decreased (P ＜ 0.01).Compared with phosgene group,the serum,BALF and lung tissue of Ang-1 and Tie-2 expressions in dexamethasone group was significantly increased (P ＜0.01).Compared with normal control group,the serum,BALF and lung tissue of Ang-2 expressions in phosgene group were significantly increased (P ＜ 0.01).Compared with phosgene group,the serum,BALF and lung tissue of Ang-2 expressions in dexamethasone group were significantly decreased (P ＜ 0.05,P ＜ 0.01).Conclusion Dexamethasone has a beneficial effect on acute lung injury induced by phosgene in rats by inhibition of Ang-2 and increase in Ang-1 and Tie-2 expressions.

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.

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.

Effects of Morroniside on Expression of Angiopoietin-1 and Tie-2 in Rats after Focal Cerebral Ischemia-reperfusion / 中国康复理论与实践

@#Objective To explore the effects of morroniside on the expression of Angiopoietin-1 (Ang-1) and Tie-2 in a rat after focal cerebral ischemia-reperfusion. Methods 20 male Sprague-Dawley rats were randomly divided into sham group (n=4), ischemia group (n=4), and morroniside groups (low, medium and high dosage groups, n=4). The middle cerebral artery were occluded for 30 min, and re-perfused. Morroniside was administered intragastrically once a day at dose of 30 mg/kg, 90 mg/kg and 270 mg/kg after operation. The expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex were detected with Western blotting analysis 7 days after operation. Results The expression of Ang-1 and Tie-2 increased in the ischemia group compared with the sham group (P<0.01), and both of them further increased in the morroniside groups of high dosage compared with the ischemia group (P<0.01), and the expression of Tie-2 also increased in the morroniside groups of medium dosage (P<0.001). Conclusion Morroniside could increase the expression of Ang-1 and Tie-2 in the ischemic ipsilateral cortex after ischemia-reperfusion in rats, suggesting promoting the angiogenesis after ischemia.

The expression changes of peripheral endothelial progenitor cells and Ang-1/Tie2 in patients with pulmonary arterial hypertension / 中华检验医学杂志

Objective To observe the expression changes of peripheral endothelial progenitor cells (EPCs) and Ang-1/Tie2 in patients with pulmonary arterial hypertension (PAH).Methods From Jun 2011 to Dec 2012,45 patients with PAH charged in Affiliated Hospital of Hangzhou Normal University were divided into 3 groups according to mean pulmonary arterial blood pressure (15 per group):mild(Group L),moderate(Group M),and severe(Group S),with another 15 normal people as control group(Group C).The EPCs were isolated from peripheral blood of every patient,number counting using fluorescence activated cell sorter (FACS),function test using cell culture in vitro.Expression of Ang-1 and Tie2 in the peripheral EPCs were measured by RT-PCR or Western-blot.Non normal data was analyzed by non parametric statistical test.Results The statistical discrepancy existed among Group L,M,S and the control in the number of EPCs [32.0 (27.0,37.0),26.0 (19.0,31.0),24.0 (22.0,26.0) vs 40.0 (37.0,51.0),P ＜ 0.05].The ability of migration [32.1 (26.5,37.5),26.8 (22.4,35.4),21.0 (17.8,34.0) vs 39.0 (33.3,42.4),P＜0.05] and adhesion of the EPCs [57.1(50.9,61.8),51.8(45.2,58.7),46.0 (37.2,55.1) vs 64.1 (56.2,75.0),P ＜ 0.05] among study groups and control group was different in statistic,the same with the proliferation activity of EPCs in different groups [0.6 (0.5,0.7),0.5 (0.4,0.6),0.4(0.3,0.5) vs 0.7(0.6,0.8),P ＜0.05].The mRNA expression of Ang-1 and Tie2 in Group M & S were significantly reduced compared with control [4.33 (2.49,4.62) and 2.89 (2.39,3.44) vs 5.31(3.78,6.22),P＜0.05],Tie2 mRNA[1.32(1.23,1.34)and 1.23(1.08,1.42)vs 1.49(1.25,1.66),P ＜ 0.05],and the protein expression of the phosphorylated Tie 2 in Group M &S were decreased [0.16 (0.15,0.24) and 0.12 (0.08,0.18) vs 0.22 (0.19,0.28),P ＜ 0.05].No significant difference of Ang-1 and Tie2 expression was observed between Group L and control [5.42 (4.72,5.95),1.54 (1.43,1.66) and0.23(0.19,0.33),P=0.674,0.867 and 0.674].Conelusion With the severity of PAH,the number and function of circulating EPCs decreased,as consistent with Ang-1 and Tie2 expression changes,suggesting that function decrease of EPCs in patients with PAH may be associated with the decrease of Ang-1/Tie2 expression.