Angiopoietins(ANGPT) and their endothelial cell-specific tyrosine kinase receptors TEK are the major regulators of blood vessels angiogenesis under physiological and pathologic conditions. ANGPT1 is essentially involved in maturation, stabilization, and remodeling of blood vessels through inducing TEK autophosphorylation, promoting endothelial cell migration and survival. Instead, ANGPT2 appears to act as a natural antagonist of ANGPT1, it can activate vascular remodeling with the presence of vascular endothelial growth factor(VEGF) or regress frank blood vessels under the absence of VEGF. High expression of angiopoietins and TEK is often detected in tumor tissues. Many studies showed that disrupting the ANGPT/TEK receptor pathway could inhibit the growth of a number of murine tumors and human tumors. Thus, it is possible that inhibitors targeting the ANGPT/TEK pathway will have broad clinical utility to treatment of cancer.
Angiopoietin-1 ; physiology ; Angiopoietin-2 ; physiology ; Angiopoietins ; physiology ; Humans ; Neovascularization, Physiologic ; physiology ; Receptor, TIE-2 ; physiology

OBJECTIVETo observe the expression of angiopoietins in oral squamous cell carcinoma and relationship between the expression of angiopoietins and pathologic classification.

METHODSThe expression of Ang-1 and Ang-2 protein in samples from 42 oral squamous cell carcinoma and 16 oral normal mucosa were detected by immunohistochemical technique.

RESULTSThe expression of Ang-1 and Ang-2 was found in both oral squamous cell carcinoma and normal control. It was found Ang-1 expression alike in oral squamous cell carcinoma and control (P > 0.05). Ang-2 expressed at low level in control while strongly positive in oral squamous cell caroinoma and the level of Ang-2 expression in oral squamous cell caroinoma was related to pathologic classification (P < 0.05).

CONCLUSIONAng-2 expression in oral squamous cell carcinoma is related to angiogenesis and pathological classification, which is probably involved in angiogenesis regulation, promotes the development and metastasis of oral squamous cell carcinoma.

Angiopoietin-1 ; Angiopoietin-2 ; Angiopoietins ; Carcinoma, Squamous Cell ; Humans ; Male ; Middle Aged ; Mouth Mucosa ; Mouth Neoplasms ; Neoplasms ; Neovascularization, Pathologic

PURPOSE: Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients. METHODS: We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression. RESULTS: IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016). CONCLUSION: A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.
Angiopoietin-1* ; Angiopoietin-2* ; Angiopoietins ; Blotting, Western ; Colorectal Neoplasms* ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Prognosis ; Receptor, TIE-2* ; Retrospective Studies

Angiopoietin-like proteins are a family of proteins that are closely related to lipid, glucose and energy metabolism, as well as angiogenesis. To date, eight Angptls have been discovered, namely Angptl1 to Angptl8 that play key roles in metabolic regulation and marker assisted selection. In this review, we summarized current progress on the structure, signaling pathways, upstream regulatory genes and metabolic network of Angptl1-8. Finally, in combination with our work, the status and problems of animal breeding as well as the future prospects for Angptls were discussed.
Angiopoietins ; genetics ; metabolism ; Animals ; Breeding ; Energy Metabolism ; Gene Regulatory Networks ; Glucose ; metabolism ; Lipid Metabolism ; Metabolic Networks and Pathways ; Signal Transduction

OBJECTIVE: To study the cytotoxicity of recombinate toxin MSH-Ang to Hep-2. METHOD: The depurated MSH-Ang were applied in cytotoxicity experiment, and the growth inhibiting action to laryngeal carcinoma cell Hep-2 were observed. RESULT: Recombination protein inhibited the growth of laryngeal carcinoma cell Hep-2, and its inhibiting action enhanced and corpuscular mortality rate increased along with the concentration increasing. CONCLUSION Recombinant toxin MSH-Ang can not only take special effect in tumors with high MSHR, but also target to many other popular tumors.
Angiopoietins ; genetics ; pharmacology ; Cell Line, Tumor ; Genetic Engineering ; Humans ; Laryngeal Neoplasms ; Melanocyte-Stimulating Hormones ; genetics ; pharmacology ; Recombination, Genetic

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.
Angiopoietins ; Endothelial Cells/metabolism* ; Humans ; Lymphatic Diseases ; Lymphatic System/metabolism* ; Receptor, TIE-2/metabolism* ; Signal Transduction ; Vascular Endothelial Growth Factor A

OBJECTIVETo investigate the changes and value of plasma angiopoietin-related growth factor (AGF) in patients with abdominal aortic aneurysm (AAA).

METHODSSerum AGF level was analyzed in 50 AAA patients and in 56 healthy subjects. AGF and adiponectin were quantified by enzyme-linked immunosorbent assay. Routine testing of blood biochemistry and high-sensitivity C-reactive protein were performed.

RESULTSThe plasma AGF level was significantly higher in AAA patients than in the controls [(87.91±96.87) μg/L vs. (56.89±41.32) μg/L, P=0.040],while serum adiponectin level showed no significant difference between these two groups. The plasma AGF level in patients with an AAA>5 cm and those with AAA between 3 cm and 5 cm were (96.08±68.61) μg/L and (75.27±46.05) μg/L.

CONCLUSIONSPlasma AGF is highly expressed in AAA patients. Higher serum AGF level is associates with larger AAA. Thus, AGF may be a potential serum biomarker for AAA.

Adiponectin ; blood ; Angiopoietin-like Proteins ; Angiopoietins ; blood ; Aortic Aneurysm, Abdominal ; blood ; Biomarkers ; blood ; C-Reactive Protein ; analysis ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Humans

BACKGROUNDA recent study reported a positive association between elevated serum levels of angiopoietin-like protein 2 (ANGPTL2) and the development of type 2 diabetes in a general population. However, the relationship of serum ANGPTL2 levels with the risk of developing gestational diabetes mellitus (GDM) has not been reported to date. The aim of this study was to investigate the change of maternal serum ANGPTL2 concentrations in the first trimester of pregnancy and to determine whether ANGPTL2 is a biomarker for subsequent GDM development.

METHODSWe conducted a prospective, nested case-control study in a pregnancy cohort. First-trimester ANGPTL2 levels were measured using a high-resolution assay in 89 women who subsequently developed GDM and in a random sample of 177 women who remained euglycemic throughout the pregnancy. Median ANGPTL2 levels were compared using Mann-Whitney U-test. Logistic regression was used to compute unadjusted and multivariable-adjusted odds ratios for developing GDM among ANGPTL2 quartiles.

RESULTSThe serum levels of ANGPTL2 was higher in women with GDM than that in women without GDM (3.06 [2.59, 3.65] ng/ml vs. 2.46 [2.05, 2.96] ng/ml, P = 0.003). Fasting blood glucose was higher in women with GDM than that in women without GDM (5.0 ± 0.9 mmol/L vs. 4.4 ± 0.6 mmol/L, P < 0.001). Glucose challenge test showed that the blood glucose was higher in women with GDM than that in women without GDM (9.1 ± 3.5 mmol/L vs. 6.2 ± 1.2 mmol/L, P < 0.001). A multivariate model adjusted for baseline characteristics, medical complications, and gestational characteristics revealed that the risk of developing GDM among women in Q4 compared with Q1 was 2.90-fold more likely to develop GDM later in pregnancy.

CONCLUSIONSAt 11-13 weeks in pregnancies that develop GDM, the serum concentration of ANGPTL2 is increased, and it can be combined with maternal factors to provide effective early screening for GDM.

Angiopoietin-like Proteins ; Angiopoietins ; blood ; Biomarkers ; blood ; Blood Glucose ; metabolism ; Case-Control Studies ; Diabetes, Gestational ; blood ; diagnosis ; Female ; Humans ; Odds Ratio ; Pregnancy ; Prospective Studies ; Risk Factors

PURPOSE: It has been reported that angiopoietins and Tie-2 receptor play an important role in the maintenance of glomerular filtration barrier in various glomerulonephritis models. We studied the role of angiopoietins on renal injury in diabetes. METHODS: In this study, we examined the changes of angiopoietin-1, angiopoietin-2, Tie-2 receptor, and nephrin expression in the experimental diabetic nephropathy and also determined whether these changes were modified by renoprotective intervention by angiotensin II receptor blocker, alpha-lipoic acid, and peroxisome proliferator activated receptor (PPAR)-agonist. RESULTS: A marked increase in urinary albumin excretion and glomerular volume was observed in diabetic rats. Renal angiopoietin-2 and Tie-2 receptor expression were significantly higher in diabetic rats than in the control groups, with a significant reduction in renal angiopoietin-2 expression, albuminuria, and renal hypertrophy in angiotensin II receptor blocker-treated diabetic rats. And there was a significant reduction in renal Tie-2 expression and renal hypertrophy in alpha-lipoic acid-treated and PPAR-gamma agonist-treated diabetic rats. CONCLUSION: These results demonstrate that the dysregulation of angiopoietins and Tie-2 receptor can lead to renal hypertrophy and albuminuria. Angiotensin II receptor blocker, alpha-lipoic acid, and PPAR-gamma agonist attenuated these changes in angiopoietins and/or Tie-2 expression and prevented the development of albuminuria and renal hypertrophy in vivo.
Albuminuria ; Angiopoietin-1 ; Angiopoietin-2 ; Angiopoietins* ; Animals ; Diabetic Nephropathies* ; Glomerular Filtration Barrier ; Glomerulonephritis ; Hypertrophy ; Peroxisomes ; Rats ; Receptor, TIE-2 ; Receptors, Angiotensin ; Thioctic Acid

OBJECTIVETo investigate the effect of ANGPTL4 gene silencing on the migration of human colon cancer cells in vitro.

METHODSThe expression of ANGPTL4 in human colorectal cancer cell lines was detected by semi-quantitative RT-PCR. Following stable transfection with a short-hairpin RNA (shRNA) targeting ANGPTL4 gene in HT29 cells, ANGPTL4 mRNA and protein expressions were detected by semi-quantitative RT-PCR and direct ELISA, respectively, and the changes in cell migration ability and cell morphology were observed with transwell and immunofluorescence assays.

RESULTSANGPTL4 was expressed in most of the colorectal cancer cell lines. Compared with the control groups, HT29 cells with shRNA-mediated ANGPTL4 gene silencing showed significantly decreased expression of ANGPTL4 mRNA and protein (P<0.05) and lowered cell migration ability possibly due to decreased pseudopodia formation.

CONCLUSIONANGPTL4 was expressed in most colorectal cancer cell lines. Decreased ANGPTL4 gene expression can inhibit the cell migration and pseudopodia formation in HT29 cells.

Angiopoietin-like 4 Protein ; Angiopoietins ; genetics ; Cell Movement ; Colorectal Neoplasms ; genetics ; pathology ; Gene Silencing ; HT29 Cells ; Humans ; RNA, Small Interfering ; genetics