Disease relevance of ANGPT1

• Depending on the cell type, expression of ANGPT1 and ANGPT2 was either activated or repressed in response to hypoxia or AdCA5 [1].
• Angiopoietin-1 promotes lymphatic sprouting and hyperplasia [2].
• Our results reinforce the concept that Ang1 therapy may be useful in settings of tissue edema [2].
• We examined the RNA content of the gene encoding angiopoietin (Ang)-2, a modifier of angiogenesis, in hepatic metastases of colorectal cancer (CRC) to explore the role of this protein in neovascularization of metastatic foci [3].
• In conclusion, consistent with the immature phenotype of the cystic epithelium, expression of VEGF, VEGFRs, Ang-1 and Tie-2 is strongly upregulated in cholangiocytes from polycystic liver diseases [4].

High impact information on ANGPT1

• However, its expression in close proximity with developing blood vessels implicates Angiopoietin-1 in endothelial developmental processes [5].
• The structure of Angiopoietin-1 differs from that of known angiogenic factors or other ligands for receptor tyrosine kinases [5].
• Although Angiopoietin-1 binds and induces the tyrosine phosphorylation of TIE2, it does not directly promote the growth of cultured endothelial cells [5].
• We report the identification of a secreted ligand for TIE2, termed Angiopoietin-1, using a novel expression cloning technique that involves intracellular trapping and detection of the ligand in COS cells [5].
• Angiopoietin-1 seems to play a crucial role in mediating reciprocal interactions between the endothelium and surrounding matrix and mesenchyme [6].

Chemical compound and disease context of ANGPT1

• CONCLUSIONS: These findings suggest that the Ang/Tie2 pathway plays a significant role in human breast tumor angiogenesis but provide no initial evidence for direct regulation of the pathway by estrogen [7].
• Angiopoietin-1 is inversely related to thymidine phosphorylase expression in human breast cancer, indicating a role in vascular remodeling [7].
• METHODS: Ang/Tie2 gene expression was assessed in rats that had been exposed to hypoxia (ie, 10% O2) for 1, 3, or 7 days [8].
• Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis [9].
• Abnormal uterine bleeding during progestin-only contraception may result from free radical-induced alterations in angiopoietin expression [10].

Biological context of ANGPT1

• Angiopoietin 1 (Ang1), a ligand for the receptor tyrosine kinase Tie2, regulates the formation and stabilization of the blood vessel network during embryogenesis [2].
• In ADPKD and control livers Ang-1 and Ang-2 gene expression was studied by real-time-PCR [4].
• Stable overexpression of Ang1 in human A431 SCCs resulted in a more than 70% inhibition of tumor growth, associated with enhanced Tie2 phosphorylation levels, as compared with low levels in control transfected tumors [11].
• We further observed cell type-specific up-regulation of the message for both angiopoietin-1 and angiopoietin-2 in gliomas [12].
• Down-regulation of angiopoietin-1 expression in menorrhagia [13].

Anatomical context of ANGPT1

• Expression of mRNA for ANGPT1 in luteal pericytes was not affected by the NO treatment [14].
• Modulation of Tie2 receptor activity by its angiopoietin ligands is crucial for angiogenesis, blood vessel maturation, and vascular endothelium integrity [15].
• We found that Ang1 activated lymphatic vessel endothelial proliferation, vessel enlargement, and generation of long endothelial cell filopodia that eventually fused, leading to new sprouts and vessel development [2].
• In this study we have demonstrated that myeloma cells express several proangiogenic factors, and, in particular, we found that angiopoietin-1 (Ang-1), but not its antagonist Ang-2, was expressed by several human myeloma cell lines (HMCLs) at the mRNA and the protein levels [16].
• In order to characterize the effects of the angiopoietins on lymphatic vessels, we employed viral vectors for overexpression of Ang1 in adult mouse tissues [2].

Associations of ANGPT1 with chemical compounds

• We also examined the effect of physiological levels of estrogen on Ang expression [7].
• Furthermore, angiopoietin-mediated PAF synthesis is partly driven by a relocalization of endogenous VEGF to the cell surface membrane [17].
• The mechanism of regulation angiopoietin mRNAs level was determined by explant culture in ambient and reduced oxygen, and in the presence of actinomycin D [18].
• These data suggest a dynamic expression of vascular-specific growth factors in a gonadotrophin-dependent, steroid-independent (VEGF) or steroid-dependent (Ang-1) manner in granulosa cells of peri-ovulatory follicles of primates [19].
• The increase of flk-1 and flt-1 (VEGF receptors) and tie-2 (Ang1 receptor) induced by ang II was significantly suppressed by PD123319 [20].
• Ang-1 induced proMMP-3 secretion from synovial cells, which resulted in direct degradation of the cartilaginous matrix [21].

Physical interactions of ANGPT1

• BACKGROUND/AIM: Angiopoietin 1 and 2 interact with vascular endothelial growth factor (VEGF) to promote angiogenesis in animal and in vitro models [22].
• TCF/LEF binding sites within the promoter region of human Angiopoietin family members were searched for by using bioinformatics and human intelligence (Humint) [23].
• ESE-1 binds to specific ETS sites within the Ang-1 promoter that are functionally important for transactivation by ESE-1 [24].
• 1 Angiopoietin-1 (Ang1) is an angiogenic growth factor that binds to the Tie2 receptor on vascular endothelium, promoting blood vessel maturation and integrity [25].
• A truncated monomeric Ang1 variant (i.e. DeltaAng1) containing the isolated fibrinogen-like receptor-binding domain of Ang1 was created and recombinantly produced in insect cells [26].

Regulatory relationships of ANGPT1

• PURPOSE: To determine whether vascular endothelial growth factor (VEGF) regulates angiopoietin (Ang)-1 and -2 expression in retinal pigment epithelial (RPE) cells [27].
• Using RT-PCR and Real-Time PCR we demonstrate that angiopoietin 2 is downregulated in human granulosa cells in vitro after choriogonadotropin treatment whereas the expression of angiopoietin 1 is not significantly altered [28].
• Angiopoietin switching regulates angiogenesis and progression of human hepatocellular carcinoma [29].
• These data indicate that VEGF-mediated disruption of endothelial cell-cell interactions requires activation of PKC beta isoforms and that this pathway is blocked by Ang1 [30].
• These novel findings suggest that angiopoietin-1 regulates expression of NERF2 and its own receptor in hypoxic cells [31].

Other interactions of ANGPT1

• Members of the vascular endothelial growth factor (VEGF) and angiopoietin family represent the most specific inducers of angiogenesis secreted by AML blasts [32].
• In contrast, angiopoietin-1 as well as angiopoietin-2 exhibit no proliferative effect on endothelial cells [33].
• Increased Tie2 expression, enhanced response to angiopoietin-1, and dysregulated angiopoietin-2 expression in hemangioma-derived endothelial cells [34].
• Ang-4 can function similarly as Ang-1 and substitute for Ang-1 to participate in hypoxia-induced angiogenesis [35].
• Immunohistochemical staining of CD34 was performed to determine the microvessel density (MVD) and Ang-2/Ang-1 ratio was calculated [36].

Analytical, diagnostic and therapeutic context of ANGPT1

• In a transwell coculture system, we observed that myeloma cells up-regulated the Ang-1 receptor Tie2 in human BM endothelial cells [16].
• Ribonuclease protection assay and Western blot analysis showed Ang-2 expression was consistently higher than Ang-1 in normal endometrium throughout the cycle [13].
• In situ hybridization and immunohistochemical studies supported these findings and revealed cyclical changes in the expression of Ang-1 and Ang-2 [13].
• We investigated the expression of Ang1 and Ang2 during multistep mouse skin carcinogenesis and in human squamous cell carcinoma (SCC) xenografts [11].
• High-power, multiple-color, immunofluorescence analyses and additional antibodies (specific for particular components of the glomerular filtration barrier) were used to determine the exact locations of Ang1 and Tie2 in the glomerular capillary wall [37].

References