Disease relevance of Angpt2

• Reciprocal regulation of angiopoietin-1 and angiopoietin-2 following myocardial infarction in the rat [1].
• CONCLUSIONS: Thus, myocardial ischemia induced by left coronary artery ligation resulted in a sustained increase in Ang-2 expression and a reciprocal decrease in Ang-1, consistent with a predominant role for Ang-2 in the angiogenic response to MI [1].
• Ang2 mRNA significantly increased from 2 weeks (2.1-fold) to 4 weeks (2.9-fold) after the infarction in the left ventricular free wall [2].
• Angiopoietin-2 and rat brain capillary remodeling during adaptation and deadaptation to prolonged mild hypoxia [3].
• CONCLUSION: The present study demonstrated cooperation between the early effect of Ang-2 and the secondary effect of VEGF to elaborate new vessels in a longitudinal study of experimental brain tumors [4].
• By using MRI and histological analysis, we studied the vascular events involved in glioma growth impairment induced by Ang2 overexpression [5].

High impact information on Angpt2

• Angiopoietin-2 (Ang2) appears to be a naturally occurring antagonist of the endothelial receptor tyrosine kinase Tie2, an important regulator of vascular stability [6].
• Destabilization of the endothelium by Ang2 is believed to potentiate the actions of proangiogenic growth factors [6].
• Inhibition of rat corneal angiogenesis by a nuclease-resistant RNA aptamer specific for angiopoietin-2 [6].
• By contrast, Ang2 promotes endothelial cell death and vessel regression if the activity of endogenous VEGF is inhibited [7].
• Angiotensin II induces expression of the Tie2 receptor ligand, angiopoietin-2, in bovine retinal endothelial cells [8].

Chemical compound and disease context of Angpt2

• Immunohistochemical study of VEGF, angiopoietin 2 and their receptors in the neovascularization following microinjection of C6 glioma cells into rat brain [4].

Biological context of Angpt2

• At the time of peak elevation in Ang-2, Tie2 phosphorylation was found to be markedly increased, consistent with receptor activation [1].
• In contrast, IGF-I, which did not significantly activate ERK or JNK, stimulated increased Ang2 expression through transcriptional activation [9].
• These data suggest that Ang2 might modulate both angiogenesis and vascular regression in the rat brain and that capillary regression occurring during deadaptation involves activation of apoptosis [3].
• Up-regulation of both Ang-2 and VEGF coincided with EC proliferation [10].
• Ang-1 and Ang-2 promote angiogenesis in this system, stimulating branching morphogenesis and mural cell assembly [11].

Anatomical context of Angpt2

• Ang-2 has been suggested to be an antagonist of TIE-2, possibly acting to release endothelial cells from the tonic stabilizing influence of Ang-1 [1].
• In the infarct territory, Ang-2 immunostaining was localized primarily to invading leukocytes at 24 h [1].
• Ang2 mRNA was increased significantly at 24 h and 48 h after reperfusion, and returned to baseline levels at 72 h, in the jeopardized myocardium [12].
• This study identifies a mechanism of growth factor-mediated reduction in Ang2 expression in vascular smooth muscle cells (VSMCs) [9].
• Endothelial Ang-1 and Tie-2 proteins were present in all cerebral vessels of normal brain including those of the choroid plexuses, whereas both these proteins as well as Ang-2 were present in choroid plexus epithelium and in ependymal cells, suggesting that angiopoietins have an autocrine effect on these cell types as well [13].

Associations of Angpt2 with chemical compounds

• Gene and protein expression of VEGF, Ang-1, and Ang-2 were increased by angiotensin II infusion [14].
• Angiotensin AT(1) and AT(2) receptors differentially regulate angiopoietin-2 and vascular endothelial growth factor expression and angiogenesis by modulating heparin binding-epidermal growth factor (EGF)-mediated EGF receptor transactivation [15].
• Recent studies have implicated the Tie2 tyrosine-kinase receptor and its main ligands--angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2)--as crucial regulators of mural cell recruitment during angiogenesis [11].
• In this study, we investigated alterations of the gene expression of Ang-1 and Ang-2 in the retinas of streptozotocin (STZ) induced diabetic rats [16].
• Of interest was the localization of both Ang1 and Ang2 in scattered PAS positive adenohypophysial cells rather than in endothelial cells [17].

Regulatory relationships of Angpt2

• In the 1 h hypoxia group, there was significant induction of Ang-2 expression (31.3% compared to its baseline control) in contrast to relatively mild Ang-1 expression (23.8% compared to its baseline control) [18].

Other interactions of Angpt2

• At 1 week, Ang-1 expression was partially restored, whereas Ang-2 expression remained elevated [1].
• In addition, immunohistochemical detection of fibronectin was used to detect BBB breakdown at the lesion site and dual labeling was used to determine whether the vessels demonstrating BBB breakdown expressed endothelial Ang-1 or Ang-2 [13].
• An apparent relationship between the expression profiles of Flk-1 and Ang-2 was observed [18].
• These cells responded chemotactically to Ang-1 and Ang-2, and secreted MMP-2 when treated with these factors [11].
• Treatment of old rats with PDGF-AB with vascular endothelial growth factor and angiopoietin-2 (a combination termed PVA), but not PDGF-AB alone, at the time of IPC decreased TNF-alpha [19].

Analytical, diagnostic and therapeutic context of Angpt2

• The ratio of Ang2/Ang1 mRNA and protein in the study group was higher than that in the control group [2].
• Immunoprecipitation showed phosphorylation of MPC Tie2 on tyrosine residues upon stimulation with Ang-1 or Ang-2 [11].
• The mRNA expression of VEGF, Ang-1, Ang-2, and their receptors was evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) [20].
• In immunohistochemistry, the vessels stained by VEGF and Ang-2 were detected in subfibrous layer [20].
• RT-PCR and western blot analyses confirmed the increase of Ang-2 expression after 6 months of diabetes [16].

References