Disease relevance of Angpt1

• In addition, Ang-1 shortened the duration of chemotherapy-induced neutropenia in wild-type mice [1].
• We addressed the effect of angiopoietin expression on tumor growth and metastasis [2].
• Angiopoietin correlates with glomerular capillary loss in anti-glomerular basement membrane glomerulonephritis [3].
• Angiopoietin/Tek interactions regulate mmp-9 expression and retinal neovascularization [4].
• In addition, COMP-Ang1 significantly decreased fasting blood glucose level, epididymal fat weight to body weight ratio, and epididymal adipocyte size in diabetic db/db mice [5].

High impact information on Angpt1

• Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche [6].
• Map3k3 disruption did not alter the expression of the genes encoding Vegf-1, angiopoietin or their receptors [7].
• Leakage-resistant blood vessels in mice transgenically overexpressing angiopoietin-1 [8].
• Targeted gene inactivation studies in mice have shown that VEGF is necessary for the early stages of vascular development and that angiopoietin-1 is required for the later stages of vascular remodeling [9].
• In fact, the expression of Angiopoietin-1, a proangiogenic soluble factor thought to mediate the mesenchymal-endothelial interactions during heart development and vascular remodeling, is down-regulated in COUP-TFII mutants [10].

Chemical compound and disease context of Angpt1

• Recombinant human Ang-1 antisense eukaryotic expression vector was constructed by directional cloning, and transfected by lipofectin method into human gastric cancer line SGC7901 with high Ang-1 expression level [11].

Biological context of Angpt1

• These findings suggest important roles for Ang signaling in the lymphatic vessel system; however, Ang function in lymphangiogenesis has not been characterized [12].
• Conversely, angiopoietin-1 (Ang-1) stimulated hematopoiesis both in wild-type and thrombopoietin-deficient mice [1].
• Expressional regulation of angiopoietin-1 and -2 and the tie-1 and -2 receptor tyrosine kinases during cutaneous wound healing: a comparative study of normal and impaired repair [13].
• CONCLUSION: We conclude that COMP-Ang1 delayed the fibrotic changes in the kidney of diabetic db/db mice through its anti-inflammatory or metabolic effects [5].
• Both IL-1beta and tumor necrosis factor-alpha caused marked down-regulation of Ang-1 mRNA levels at 4 h with a further decrease observed at 24 h [14].

Anatomical context of Angpt1

• In this study, we reveal that lymphatic vascular endothelial hyaluronan receptor 1-positive (LYVE-1(+)) lymphatic endothelial cells (LECs) express Tie2 in both embryonic and adult settings, indicating that Ang signaling occurs in lymphatic vessels [12].
• Angiopoietin-1 promotes LYVE-1-positive lymphatic vessel formation [12].
• We found that human umbilical vein endothelial cells treated with Ang1 produce ROS transiently, which was suppressed by NADPH oxidase inhibitor, diphenylene-iodonium chloride, and rotenone [15].
• It has become evident that a closely regulated presence of vascular endothelial growth factor (VEGF) and angiopoietin (Ang) factors determines the fate of blood vessel formation during angiogenesis [13].
• RESULTS: COMP-Ang1 reduced albuminuria and decreased mesangial expansion, thickening of the glomerular basement membrane and podocyte foot process broadening and effacement [5].

Associations of Angpt1 with chemical compounds

• Here, we demonstrate that angiopoietin/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains-2 (Tie2) signaling contributes to the assembly and remodeling of BM neovessels after myelosuppression [1].
• Hydrogen peroxide produced by angiopoietin-1 mediates angiogenesis [15].
• Thirty minutes of pretreatment with the NADPH oxidase inhibitors diphenylene iodinium (DPI, 10 muM) and apocynin (200 muM) suppressed Ang-1-stimulated ROS [16].
• After intraperitoneal glucose challenge, COMP-Ang1 significantly lowered plasma glucose levels [5].
• Examination of the uteri revealed Ang-2 mRNA and protein expression in the oestrogen-dominated cycling phase and the progesterone-dominated mated phase, whereas Ang-1 expression was restricted to the mated phase [17].

Physical interactions of Angpt1

• The effects of inhibiting angiopoietin binding to the Tie-2 receptor was studied in newborn mice with experimentally induced retinal neovascularization [4].
• Ang-1 exerts its biological effects by binding to the EC-specific tyrosine kinase receptor Tie-2, and initiates intracellular signaling in ECs [14].

Regulatory relationships of Angpt1

• On the basis of these observations, we propose that Ang signaling regulates lymphatic vessel formation through Tie2 [12].
• Because pericytes play a role in regulating EC function, we also determined whether IL-1beta would also down-regulate Ang-1 in human vascular smooth muscle cells [14].
• The angiopoietin families of vascular regulators and their receptors were expressed at much higher levels than the VEGFs and their receptors and while the angiopoietins showed diminished or delayed expression in the absence of TNF-alpha signaling, VEGF and its receptors remained unaltered [18].
• Ang-1 activates the endothelial cell-specific tyrosine kinase receptor Tie-2, which in turn leads to enhanced endothelial cell survival and stabilization [19].
• Expression of angiopoietin 1 blocked the increased leakiness of the blood vessels induced by VEGF-C whereas vessel enlargement and lymphangiogenesis were not affected [20].

Other interactions of Angpt1

• Expression of angiopoietin-1, angiopoietin-2, and the Tie-2 receptor tyrosine kinase during mouse kidney maturation [21].
• Expressional regulation of the angiopoietin-1 and -2 and the endothelial-specific receptor tyrosine kinase Tie2 in adrenal atrophy: a study of adrenocorticotropin-induced repair [22].
• Modulation of the angiogenesis response through Ha-ras control, placenta growth factor, and angiopoietin expression in mouse skin carcinogenesis [23].
• Exogenous VEGF-A and Ang-1 stimulated Tie2 expression in the BM vasculature [1].
• To address our hypothesis, we assessed protein levels of endothelial cell-selective angiogenic factors: angiopoietin (ANG)-1, vascular endothelial growth factor (VEGF), and mediator of VEGF signaling, VEGF receptor-2 [fetal liver kinase (Flk)-1], a transmembrane receptor tyrosine kinase [24].

Analytical, diagnostic and therapeutic context of Angpt1

• METHODS: Reverse transcriptase-polymerase chain reaction (RT-PCR) as well as Southern blotting was used to determine the ontogeny of angiopoietin-1 and angiopoietin-2 gene expression in the embryonic mouse pancreas and lung [25].
• Expression of vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in tumors was examined by Western blotting [26].
• Direct effects of recombinant Ang-1 on angiogenesis were studied with an in vivo Gelfoam angiogenesis assay [19].
• Inhibition of angiopoietin-1 expression in tumor cells by an antisense RNA approach inhibited xenograft tumor growth in immunodeficient mice [27].
• Expression of VEGF and Angiopoietin-1 and Angiopoietin-2 protein by murine neutrophils was evaluated by confocal immunohistochemistry [28].

References