Disease relevance of ANGPT2

• Depending on the cell type, expression of ANGPT1 and ANGPT2 was either activated or repressed in response to hypoxia or AdCA5 [1].
• In conclusion, the current study suggests that Ang-2 and VEGF may cooperate to enhance the formation of new blood vessels in metastases of CRC to the liver [2].
• Analysis of concerted expression of angiogenic growth factors in acute myeloid leukemia: expression of angiopoietin-2 represents an independent prognostic factor for overall survival [3].
• We further observed cell type-specific up-regulation of the message for both angiopoietin-1 and angiopoietin-2 in gliomas [4].
• Small capillaries with few periendothelial support cells showed strong expression of Angiopoietin-2, whereas larger glioblastoma vessels with many periendothelial support cells showed little or no expression [4].
• Immunohistochemical analysis of HER2 and Ang-2 proteins in human breast carcinomas shows that Ang-2 expression in breast cancer correlates with HER2 expression [5].
• Hypoxia augmented the inhibitory effect of Ang-2 on the release of the anti-angiogenic cytokine, IL-12 by monocytes [6].
• Hypoxia up-regulates Tie2 expression on TEMs and, together with Ang-2, down-regulates their antitumor functions [7].
• Induction of Ang-2 in neuroendocrine tumors represents a clinically relevant pathomechanism of disease progression and constitutes an adverse prognostic marker [8].

High impact information on ANGPT2

• Methylglyoxal modification of mSin3A links glycolysis to angiopoietin-2 transcription [9].
• The lymphangiogenic molecules VEGF-D and angiopoietin-2 were elevated in the plasma of individuals with acquired immune deficiency syndrome and Kaposi sarcoma [10].
• The angiogenic growth factor angiopoietin 2 (Ang2) destabilizes blood vessels, enhances vascular leak and induces vascular regression and endothelial cell apoptosis [11].
• Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death [11].
• We use RNA interference to demonstrate that FKHR is required for the expression of genes (including Ang-2) that have important vascular functions [12].

Chemical compound and disease context of ANGPT2

• Expression of angiopoietin-1, angiopoietin-2, and Tie2 genes in normal ovary with corpus luteum and in ovarian cancer [13].
• There were no statistically significant effects of laser photocoagulation on plasma VEGF, Ang-2, and tie-2 in the 19 patients with PDR, or any effects of eprosartan in the 28 patients with non-proliferative diabetic retinopathy [14].
• Plasma vascular endothelial growth factor, angiopoietin-2, and soluble angiopoietin receptor tie-2 in diabetic retinopathy: effects of laser photocoagulation and angiotensin receptor blockade [14].
• In FNH, Ang-1 was significantly up-regulated, Ang-2 was down-regulated, and the Ang-1/Ang-2 ratio was highly and specifically increased in FNH compared with normal liver or other groups of lesions (FNH, 15.2-fold increase; HCC, 2.78; adenoma, 2.28; cirrhosis, 1.92; P < 0.01 for FNH vs. all groups, analysis of variance) [15].
• Hypoxia-inducible angiopoietin-2 expression is mimicked by iodonium compounds and occurs in the rat brain and skin in response to systemic hypoxia and tissue ischemia [16].

Biological context of ANGPT2

• In ADPKD and control livers Ang-1 and Ang-2 gene expression was studied by real-time-PCR [17].
• To test the hypothesis that menorrhagia arises as a result of poor signal for vascular maturation, we have examined the expression of Ang-1, Ang-2, and Tie-2 in endometrium throughout the menstrual cycle from 30 normal women and 28 patients with menorrhagia [18].
• Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway [19].
• Ang-2 treatment had no effect on cell migration and in vitro wound healing but significantly attenuated serum deprivation-induced apoptosis and promoted survival [20].
• MATERIALS AND METHODS: The mRNAs encoding Ang-1, Ang-2, and Tie-2 were detected and localized in human placentae throughout gestation [21].

Anatomical context of ANGPT2

• CONCLUSION(S): The ratio of ANGPT2/ANGPT1 mRNA in endometrial grafts increased after 24 hours of cultivation on the chicken chorioallantoic membrane and shows a shift toward a more dominant role of ANGPT2 [22].
• Ribonuclease protection assay and Western blot analysis showed Ang-2 expression was consistently higher than Ang-1 in normal endometrium throughout the cycle [18].
• In this study, we evaluated signaling pathways and biological effects of physiological concentrations of Ang-2 in cultured human umbilical vein endothelial cells [20].
• RESULTS: In situ hybridization showed that Ang-2 mRNA was abundant in the syncytiotrophoblast in the first trimester of human pregnancy [21].
• Ang-2 was expressed predominately in prostate epithelial cells whereas Ang-1 was expressed in epithelium and smooth muscle [23].

Associations of ANGPT2 with chemical compounds

• Steroid ablation decreased (P < 0.05) Ang-1 mRNA at 36 h, and Ang-2 mRNA at 12 h, while only Ang-1 was restored by progestin replacement [24].
• Tumor necrosis factor-alpha upregulates angiopoietin-2 in human umbilical vein endothelial cells [25].
• Therefore, VEGF/Ang-2 ratio after BDP therapy was markedly decreased to the same level as in the control subjects [26].
• Relationship between vascular endothelial growth factor and angiopoietin-2 in asthmatics before and after inhaled beclomethasone therapy [26].
• These increases in angiopoietin-2 and Tie2 receptor proteins at 6 h were blocked by the addition (30 min before stretch) of the protein kinase C inhibitor Gö6976 (16 nM) or the tyrosine kinase inhibitor herbimycin A (24 microM) [27].

Physical interactions of ANGPT2

• Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition [28].

Regulatory relationships of ANGPT2

• Angiopoietin 2 was expressed by endothelial cells in the vicinity of the proliferating epidermis that abundantly expressed vascular endothelial growth factor [29].
• 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 [30].
• Both Angio2-mediated events were abrogated by expressing a dominant negative STAT5 construct (DeltaSTAT5) [31].
• The Ang-2 gene is upregulated in the hypervascular type of human hepatocellular carcinoma (HCC) [32].
• CONCLUSIONS: PTH upregulates Ang-2 upon explantation, with peak protein production by 24 hours [33].

Other interactions of ANGPT2

• Western blot analysis suggested that expression of Ang-1, Ang-2, Tie-2, and VEGF may be regulated at a transcriptional level [2].
• Although the function of Tie2 and its ligands in tumor angiogenesis remains a subject of speculation, our findings are in agreement with a recently proposed hypothesis that in the presence of VEGF, local production of Ang-2 might promote angiogenesis [4].
• Intensive multifactorial intervention is associated with reductions in plasma VEGF, vWf, and (in patients without CVD) Ang-2 levels, possibly reflecting an improved vascular profile with treatment [34].
• Consistent with the expression of Angio2 in neovessels of advanced lesions a transcriptionally active STAT5 was detected [31].
• Angiopoietin-1, unlike angiopoietin-2, is incorporated into the extracellular matrix via its linker peptide region [35].

Analytical, diagnostic and therapeutic context of ANGPT2

• In situ hybridization and immunohistochemical studies supported these findings and revealed cyclical changes in the expression of Ang-1 and Ang-2 [18].
• Citrated plasma was analyzed for Ang-1, Ang-2, tie-2, and VEGF by enzyme-linked immunosorbent assay [36].
• In patients treated by curative surgery, patients with tumors showing both positive-Ang-2 and positive-VEGF condition at the deepest invasive tumor site had significantly poorer prognoses than patients with tumors under other conditions [37].
• The expression of Angiopoietin-1, Angiopoietin-2, and their receptor Tie-2 in HCC was assessed by immunohistochemistry [38].
• METHODS: The expression of Angiopoietin-1 and Angiopoietin-2 mRNAs in cultured hepatoma cells under hypoxic conditions and in HCC and noncancerous liver tissue was evaluated by real-time PCR [38].

References