Angiopoietin-1 ; chemistry ; physiology ; Angiopoietin-2 ; chemistry ; physiology ; Angiopoietins ; physiology ; Animals ; Cardiovascular Diseases ; therapy ; Embryonic and Fetal Development ; Humans ; Neoplasms ; blood supply ; Receptor, TIE-2 ; chemistry ; physiology ; Signal Transduction

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.
Angiopoietin-1* ; Angiopoietin-2* ; Animals ; Blood-Brain Barrier ; Blotting, Western ; Brain ; Brain Injuries ; Capillary Permeability ; Evans Blue ; Hippocampus ; Immunohistochemistry ; Microvessels ; Permeability ; Punctures ; Rats ; Subarachnoid Hemorrhage*

Adult ; Aged ; Angiopoietin-2 ; physiology ; Female ; Glioma ; blood ; physiopathology ; Humans ; Hypoxia ; blood ; metabolism ; Male ; Middle Aged ; Neovascularization, Pathologic ; physiopathology

BACKGROUNDAngiopoietin-2 (Ang-2) plays a crucial role in hypoxia-induced angiogenesis and is expressed only in sites of vascular remodeling. Ang-2 expression can be regulated by hypoxia inducible factors and other regulators with exposure to hypoxia. The objective of this study was to investigate the influence of percutaneous coronary intervention (PCI) on serum Ang-2 concentrations, and analyze the correlation between serum Ang-2 and the severity of coronary artery stenosis in patients with coronary heart disease (CHD).

METHODSSixty-four patients with CHD were selected as the study group, each undergone PCI. Thirty-two healthy subjects were selected as the control group. Pre-PCI and post-PCI serum Ang-2 were measured by enzyme-linked immunosorbent assay. The severity of coronary artery stenosis was evaluated using angiographic Gensini scores, and the coronary collateral vessels were scored according to Rentrop's classification.

RESULTSConcentrations of pre-PCI serum Ang-2 in the study group were significantly higher than those in the control group (4625.06 ± 1838.06 vs. 1945.74 ± 1588.17 pg/ml, P < 0.01); however, concentrations of post-PCI serum Ang-2 were significantly lower than those of pre-PCI (3042.63 ± 1845.33 pg/ml vs. 4625.06 ± 1838.06 pg/ml, P < 0.01). Concentrations of pre-PCI serum Ang-2 were significantly correlated with Gensini scores (r = 0.488, P < 0.01); however, the decrease in serum Ang-2 after PCI was not correlated with Gensini scores, coronary collateral vessel grading, or left ventricular ejection fraction.

CONCLUSIONSSerum Ang-2 concentrations significantly increased in patients with CHD, and PCI treatment significantly decreased these concentrations. Serum Ang-2 concentrations, but not the decrease in serum Ang-2 concentrations, were significantly correlated with the severity of coronary artery stenosis. These results suggested that Ang-2 may be a biomarker of myocardial ischemia and vessel remodeling.

Adult ; Angiopoietin-2 ; blood ; Coronary Artery Disease ; blood ; therapy ; Female ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention

PURPOSE: Vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) are major mediators of angiogenesis and are induced by tissue inflammation and hypoxia. The purpose of this study was to investigate whether serum VEGF and Ang-2 are associated with the presence of hemoptysis and the extent of systemic inflammation in patients with inflammatory lung diseases. MATERIALS AND METHODS: We prospectively enrolled 52 patients with inflammatory lung disease between June 2008 and October 2009. RESULTS: The median values of VEGF and Ang-2 were 436 pg/mL and 2383 pg/mL, respectively. There was a significant positive correlation between serum Ang-2 and VEGF levels. VEGF levels were not significantly different according to the presence of hemoptysis. C-reactive protein (CRP) and Ang-2 level were significantly higher in patients without hemoptysis (n=26) than in those with hemoptysis (n=26; p<0.001 and p<0.001, respectively). CRP and arterial oxygen tension (PaO2) were significantly correlated with both serum VEGF (p=0.032 and p=0.016, respectively) and Ang-2 levels (p<0.001 and p=0.041, respectively), after adjusting for other factors. Age and the absence of hemoptysis were factors correlated with serum Ang-2 levels CONCLUSION: Our study suggests that serum VEGF and Ang-2 levels are associated with PaO2 and the severity of inflammation rather than the presence of hemoptysis in patients with inflammatory lung diseases. Thus, hemoptysis may not be mediated by increased serum levels of VEGF and Ang-2 in patients with inflammatory lung diseases, and further studies are required to determine the mechanisms of hemoptysis.
Aged ; Angiopoietin-2/*blood ; Female ; Hemoptysis/*blood ; Humans ; Inflammation/*blood ; Lung Diseases/*blood ; Male ; Middle Aged ; Prospective Studies ; Vascular Endothelial Growth Factor A/*blood

OBJECTIVETo explore the effects of angiopoietins (Ang-1 and Ang-2) and Tie-2 expression on microvessel density (MVD) in gastric cancers.

METHODSBy using semiquantitative RT-PCR, immunohistochemistry and image analysis system, the expression of Ang-1, Ang-2, Tie-2 mRNA and their proteins were detected in 68 primary gastric cancers and their adjacent normal tissues. Microvessel density (MVD) was figured out based on CD34 immunohistochemical staining.

RESULTSThe expression of all Ang-1, Ang -2, Tie-2 mRNA and their proteins was detected in gastric cancers and their paired adjacent gastric mucosa tissues. A negative correlation between Ang-1 protein, Tie-2 mRNA and MVD in gastric cancers was observed (r = -0.440, r = -0.267; P < 0.05), while the relation between Ang-2 mRNA and its protein, Ang-2/Ang-1 protein ratio with MVD were positive (r = 0.319, r = 0.729, r = 0.739; P < 0.05). It was found that MVD in groups with Ang-2 mRNA T/N ratio over 1.2 (the ratio of Ang-2 mRNA in gastric cancers and its adjacent normal mucosa) was higher than that in those with a ratio under 1.2, revealed by analysing the effects of Ang-1 and Ang-2 mRNA T/N ratio on MVD in gastric cancers.

CONCLUSIONAng-1 activates Tie-2 receptor, whereas Ang-2 antagonizes Ang-1 in the angiogenesis, and the Ang-2/Ang-1 ratio determines angiogenesis and tumor growth in gastric cancers. When the expression of Ang-2 is high and Ang-1 is low, the angiogenesis in gastric cancers is promoted, otherwise oppositely. The role of Ang-2 is dominant in the effect of Angs and their receptor on angiogenesis in gastric cancers.

Angiopoietin-1 ; biosynthesis ; genetics ; Angiopoietin-2 ; biosynthesis ; genetics ; Female ; Humans ; Male ; Microcirculation ; pathology ; Middle Aged ; Neoplasm Staging ; Neovascularization, Pathologic ; etiology ; RNA, Messenger ; biosynthesis ; genetics ; Receptor, TIE-2 ; biosynthesis ; genetics ; Stomach Neoplasms ; blood supply ; metabolism ; pathology

OBJECTIVETo investigate the expression of angiopoietin (Ang)-1 and Ang-2 in colorectal tumors and its relations to microvessel density (MVD) in tumor tissue.

METHODSAng-1, Ang-2 and factor VIII-related antigen were stained immunohistochemically in 91 cases of primary colorectal adenocarcinoma, 20 cases of colorectal adenoma and 24 cases of normal colorectal mucosal tissue, and MVD was also assayed in above tissue specimens.

RESULT(1) A significantly higher Ang-1 (7.07+/-2.00) was observed in normal tissue compared with 1.75 +/-1.98 in the adenoma and 1.40 +/- 1.22 in the adenocarcinoma (P<0.01). (2) Ang-2 protein positive rate in adenocarcinoma was significantly higher than that in normal tissue and adenoma (P<0.01). The expression of Ang-2 in adenocarcinoma was closely associated with poor differentiation and vessel invasion. (3) There were significant correlations between Ang-1 and Ang-2 (r=-0.338, P<0.01), Ang-1 and MVD (r=-0.388, P<0.01), Ang-2 and MVD (r=0.594, P<0.01) in the 135 cases.

CONCLUSIONThe overexpression of Ang-2 may play an important role in angiogenesis of colorectal adenocarcinoma. It can be regarded as an index for malignancy and prognosis in colorectal adenocarcinoma.

Adenocarcinoma ; blood supply ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Angiopoietin-1 ; biosynthesis ; genetics ; Angiopoietin-2 ; biosynthesis ; genetics ; Biomarkers, Tumor ; Capillaries ; pathology ; Colorectal Neoplasms ; blood supply ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; von Willebrand Factor ; biosynthesis ; genetics

OBJECTIVE: To investigate the expression of Angiopoietin-1,2 in laryngeal squamous cell carcinoma (LSCC) and the relationship between Angiopoietin-1,2 expression and clinicopathologic parameters and microvessel density (MVD) marked by CD105, and also evaluate the significance of co-expression of Ang-2 and vascular endothelial cell growth factor (VEGF) in tumor angiogenesis. METHOD: The expression of Ang-1,2 and VEGF in samples of tumor, para cancer and normal mucosa were detected by immunohistochemical method. RESULT: The expression of Angiopoietin-1,2 were identified in LSCC, para cancer tissue and normal mucosa. The VEGF expression was only existed in LSCC. The expression of Ang-1,2 were significantly higher in LSCC than in para cancer tissue (P < 0.05) and normal mucosa (P < 0.01). In the clinicopathologic parameters, only the expression of Ang-2 was closely correlated with clinical stages and MVD (all P < 0.05). There was no significant correlation between the expression of Ang-1,2 and tumor differentiation degree (all P > 0.05). When the expression of Ang-2 and VEGF were both positive, the mean value of MVD was higher than others (P < 0.05). CONCLUSION These results suggest that overexpression of Ang-1,2 may play a very important role in the development of LSCC and are closely correlated with angiogenesis. Ang-2 promote angiogenesis when interacting with VEGF.
Aged ; Angiopoietin-1 ; metabolism ; Angiopoietin-2 ; metabolism ; Carcinoma, Squamous Cell ; blood supply ; metabolism ; pathology ; Female ; Humans ; Laryngeal Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Microcirculation ; Middle Aged ; Neovascularization, Pathologic ; Vascular Endothelial Growth Factor A ; metabolism

BACKGROUNDAngiopoietin-2 (Ang-2) is one of the critical regulators of tumor angiogenesis. Studies have shown a significant correlation of Ang-2 expression to tumor invasion and metastasis in various human cancers, but little is known about the serum Ang-2 (sAng-2) levels in esophageal squamous cell cancer (ESCC) and its precursors. In this study, we aimed to investigate its role in screening for ESCC and its precursors.

METHODSWe carried out a free endoscopic screening in Feicheng City, a high ESCC incidence area in Shandong Province of China. Serum samples were collected as follows: 91 from normal subjects, 44 from patients with esophagitis, 85 from patients with hyperplasia, and 13 from patients with early ESCC. In addition, 28 serum samples were obtained from patients with invasive ESCC undergoing surgery in People's Hospital of Feicheng City. All the subjects of the five groups were diagnosed by histopathology. The sAng-2 levels were tested and compared, and the diagnostic power in early or/and invasive ESCC was calculated in terms of sensitivity and other parameters.

RESULTSThe sAng-2 levels were (22.0 +/- 5.5), (21.3 +/- 3.2), (20.5 +/- 3.3), (24.0+/- 5.0), and (29.8 +/- 5.0) U/ml in normal, esophagitis, hyperplasia, early ESCC, and invasive ESCC groups respectively. It was significantly higher in early ESCC than inhyperplasia group (P = 0.009). The invasive ESCC group showed the highest Ang-2 level among all groups (all P = 0.000). The sensitivities of sAng-2 to early and invasive ESCC were 23.1% and 78.6% respectively.

CONCLUSIONsAng-2 level is related to carcinogenesis and progression of ESCC, but it can not be used to screen for early ESCC.

Aged ; Angiopoietin-2 ; blood ; genetics ; Carcinoma, Squamous Cell ; blood ; diagnosis ; Esophageal Neoplasms ; blood ; diagnosis ; Female ; Humans ; Male ; Middle Aged ; RNA, Messenger ; analysis

OBJECTIVE: To investigate the relationship between the expression of Ang2, Tie2 and the angiogenesis of hepatocellular carcinoma in rats. METHODS: Thirty-eight healthy male rats were randomly divided into 3 groups: 5 rats in the control group; 25 rats in the experimental group were equally divided into 5-day, 10-day, 15-day, 20-day, and 25-day groups; the other 8 rats were used as the supplement of the experimental group. An allogenic transplanted rat model of CBRH-7919 hepatocellular carcinoma in situ was established by immunosuppression. The expressions of Ang2 and Tie2 were detected by immunohistochemical staining in cancerous tissues of different developmental stages and liver tissues of the control group. At the same time, microvessel density was determined by anti-CD31 immunohistochemical staining. RESULTS: CBRH-7919 hepatocellular carcinoma models were successfully set up in 24 rats. The expression level of Ang2 and Tie2 in cancerous tissues was much higher than that of liver tissues of the control group (P <0.05). The overexpression of Ang2 was pristine and continuous in different developmental stages. The expressions of Ang2 and Tie2 positively correlated with microvessal density in hepatocellular carcinoma (P<0.05). CONCLUSION The up-regulation of Ang2 and Tie2 may play important roles in the angiogenesis of hepatocellular carcinoma. Ang2 may participate in the start of angiogenesis of hepatocellular carcinoma.
Angiopoietin-2 ; biosynthesis ; genetics ; Animals ; Liver Neoplasms, Experimental ; blood supply ; metabolism ; Male ; Neovascularization, Pathologic ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, TIE-2 ; biosynthesis ; genetics