Disease relevance of Angpt1

• OBJECTIVE: This study sought to characterize changes in the angiopoietin system in a rat model of myocardial infarction (MI) [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].
• Thus Ang-1 therapy may have therapeutic potential in reducing BBB breakdown and the ensuing edema after massive brain injury [2].
• CONCLUSION: These results demonstrate that infusion of exogenous Ang II starting prior to the induction of nephritis activates VEGF and Ang-1 signaling regulated via both Ang II receptors, potentially leading to the accelerated recovery of injured glomerular endothelial cells in the early phase of anti-Thy-1.1 nephritis [3].
• RESULTS: Using in situ hybridization analysis, Ang-1, Ang-2, and Tie2 mRNA expression was observed in the ganglion cell layer (GCL) and the inner nuclear layer (INL) [4].

High impact information on Angpt1

• In vitro PDGF-AB induced vascular endothelial growth factor (VEGF) and angiopoietin (Ang)-2 expression in 4-mo-old rat cardiac endothelial cells, but not in 24-mo-old heart cells [5].
• Retinal angiogenesis is mediated by an interaction between the angiotensin type 2 receptor, VEGF, and angiopoietin [6].
• Suppression of diabetic retinopathy with angiopoietin-1 [7].
• Expression of angiopoietin-1, angiopoietin-2, and tie receptors after middle cerebral artery occlusion in the rat [8].
• To assess the role of the angiopoietin/tie family in ischemia-triggered angiogenesis we analyzed their temporal and spatial expression pattern after middle cerebral artery occlusion (MCAO) using in situ hybridization and immunohistochemistry [8].

Chemical compound and disease context of Angpt1

• The purpose of this study was to evaluate the expression of Tie-2 and Ang-1 and -2 in an acetic acid-induced gastric ulcer healing process in rats [9].
• Angiopoietin-1 increases arteriolar vasoconstriction to phenylephrine during sepsis [10].

Biological context of Angpt1

• This study demonstrates that Ang-1 is an important factor in maintaining normal homeostasis in the brain [2].
• Neutralizing anti-HB-EGF antibody blocked EGFR phosphorylation by Ang II [11].
• Thus, Ang II is involved in the VEGF-Ang-Tie2 system via HB-EGF-mediated EGFR transactivation, and this link should be considerable in pathological conditions in which collateral blood flow is required [11].
• Ang-1 and Ang-2 promote angiogenesis in this system, stimulating branching morphogenesis and mural cell assembly [12].
• 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 [4].

Anatomical context of Angpt1

• In situ hybridization and immunohistochemical studies localized VEGF, Ang-1, and Ang-2 expression to the epithelial cells of the glomerulus, and VEGF-R2 and Tie-2 receptors to the endothelial cells of the kidney [13].
• Immunohistochemical staining revealed Ang-1 and TIE-2 immunoreactivity localized to vascular endothelium [1].
• RESULTS: At 24 h, Ang-1 mRNA and protein expression within the infarct and peri-infarct regions were decreased compared to non-infarcted myocardium, whereas Ang-2 mRNA levels were markedly increased and TIE-2 expression was unchanged [1].
• 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 [2].
• Modulation of Tie2 receptor activity by angiopoietin ligands is crucial for angiogenesis, blood vessel maturation, and vascular endothelium integrity [14].

Associations of Angpt1 with chemical compounds

• Gene and protein expression of VEGF, Ang-1, and Ang-2 were increased by angiotensin II infusion [13].
• Estradiol regulates angiopoietin-1 mRNA expression through estrogen receptor-alpha in a rodent experimental stroke model [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 [12].
• Ang-1 gene transfer attenuated the LPS-induced increases in ppET-1 RNA and lavage ET-1 protein by 34% and 33%, respectively (P < 0.05) [16].
• Neutralizing Ang1 antibody attenuates DETA-NONOate-induced capillary tube formation [17].

Physical interactions of Angpt1

• A pericyte-derived angiopoietin-1 multimeric complex induces occludin gene expression in brain capillary endothelial cells through Tie-2 activation in vitro [18].

Regulatory relationships of Angpt1

• 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 [2].
• Ang II also upregulated vascular endothelial growth factor (VEGF) expression in an HB-EGF/EGFR-dependent manner [11].
• PCT-CM-induced occludin up-regulation was significantly inhibited by an angiopoietin-1-neutralizing antibody, whereas the up-regulation by AST-CM was not [18].
• We conclude that Ang-1 promotes neurite outgrowth from DRG cells positive for Tie-2 receptor [19].
• 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) [20].

Other interactions of Angpt1

• Ang-1 and Ang-2 gene but not protein expression were reduced by both treatments [13].
• RESULTS: Diabetes was associated with increased gene and protein expression of VEGF, VEGF-R2, Ang-1, Ang-2 and Tie-2 [21].
• These cells responded chemotactically to Ang-1 and Ang-2, and secreted MMP-2 when treated with these factors [12].
• Immunoprecipitation and western blot analyses confirmed that multimeric angiopoietin-1 is secreted from TR-PCT1 cells, and induces occludin mRNA, acting through tyrosine phosphorylation of Tie-2 in TR-BBB13 cells [18].
• Real-time PCR was used to measure steady state mRNA expression of VEGF, VEGFR-2, angiopoietin-1, and Tie2 [22].

Analytical, diagnostic and therapeutic context of Angpt1

• The role of the angiopoietin/Tie receptor system in myocardial ischaemia/reperfusion is not well known [23].
• Immunoprecipitation showed phosphorylation of MPC Tie2 on tyrosine residues upon stimulation with Ang-1 or Ang-2 [12].
• RESULTS: Expression of Tie-2 and Ang-1 and -2 mRNAs was detected in normal gastric tissue and ulcerative tissues by RT-PCR [9].
• RESULTS: Pulmonary artery pressures of AAV-Ang-1 injected rats were significantly increased compared with the control groups (p < 0.01) at all timepoints [24].
• We hypothesized that targeted overexpresssion of angiopoietin-1 in the lung would cause persistent pulmonary hypertension in an animal model [24].

References