Disease relevance of Ang2

• The enhanced Ang2 expression following VEGF stimulation and hypoxia was accompanied by de novo protein synthesis as detected by immunoprecipitation [1].
• In a mouse model of ischemia-induced retinal neovascularization, Ang2 mRNA was up-regulated in the ischemic inner retinal layer, and remarkable expression was observed in neovascular vessels [1].
• Ang2 is thus a mediator of epithelial necrosis with an important role in hyperoxic ALI and pulmonary edema [2].
• Ang2 in plasma and alveolar edema fluid is increased in adults with ALI and pulmonary edema [2].
• We considered that Ang2 might be important in hyperoxic acute lung injury (ALI) [2].

High impact information on Ang2

• This modification of Sp3 causes decreased binding of the repressor complex to a glucose-responsive GC box in the angiopoietin-2 promoter, resulting in increased Ang-2 expression [3].
• The angiogenic growth factor angiopoietin 2 (Ang2) destabilizes blood vessels, enhances vascular leak and induces vascular regression and endothelial cell apoptosis [2].
• Here we have characterized the responses in lungs induced by hyperoxia in wild-type and Ang2(-/-) mice or those given either recombinant Ang2 or short interfering RNA (siRNA) targeted to Ang2 [2].
• Ang2 increases inflammation and cell death during hyperoxia in vivo and stimulates epithelial necrosis in hyperoxia in vitro [2].
• During hyperoxia Ang2 expression is induced in lung epithelial cells, while hyperoxia-induced oxidant injury, cell death, inflammation, permeability alterations and mortality are ameliorated in Ang2(-/-) and siRNA-treated mice [2].

Chemical compound and disease context of Ang2

• In mice with ubiquitous doxycycline-inducible expression of Ang2, in the absence of doxycycline, intravitreous injection of a gutless adenoviral vector expressing VEGF (AGV.VEGF) resulted in neovascularization of the cornea and iris, but no retinal neovascularization [4].
• These data establish a functional link between Ang2 interaction with alpha(v)beta(1) integrin and glioma cell invasion through the FAK/p130(Cas)/ERK1/2 and JNK-mediated signaling pathway [5].

Biological context of Ang2

• Understanding the regulation of macrophage Ang2 production is especially important in an effort to target the pathologic role of macrophages while preserving their role in immunity and homeostasis [6].
• The mouse angiogenin gene family: structures of an angiogenin-related protein gene and two pseudogenes [7].
• Hyperoxia induces and activates the extrinsic and mitochondrial cell death pathways and activates initiator and effector caspases through Ang2-dependent pathways in vivo [2].
• METHODS: We examined the combination effect of VEGF and Ang-2 overexpression by means of a combination of a retroviral tetracycline (tet) regulated gene manipulating system in vivo, by providing tet in the drinking water, and a conventional plasmid gene expression system [8].
• Ang2 showed no effect on proliferation, but stimulated chemotaxis and tube-like structure formation [9].

Anatomical context of Ang2

• In adults, Ang1 is associated with blood vessel stabilization and recruitment of perivascular cells, whereas Ang2 acts to counter these actions [10].
• VEGF induced both a time- and concentration-dependent increase in angiopoietin-2 (Ang2) mRNA expression in bovine microvascular endothelial cells [1].
• The abnormal lymphatic periendothelial cells were considered to be a type of pericyte for the lymphatic capillaries after the deletion of Ang2, because they were ultrastructurally characterized by abundant thin myofilaments in their cytoplasm and long cytoplasmic extensions similar to those shown by blood vascular pericytes [11].
• Since stimulation of the PKA pathway can lead to macrophage production of VEGF, it is possible that enhancement of Ang2 production by macrophages may be due to autocrine responsiveness to VEGF [6].
• Ang2 expression in the highly proliferative tumor vascular endothelium was also increased, as was phosphorylated Tie2/Tek [12].

Associations of Ang2 with chemical compounds

• Cyclic AMP-dependent protein kinase (PKA) played a major role in this enhancement since the PKA inhibitor, H89, blocked secretion of Ang2 [6].
• The secretion of Ang2 was enhanced by treatment with lipopolysaccharide, interferon-gamma, prostaglandin E2 and other cyclic AMP-elevating agents, as well as vascular endothelial growth factor (VEGF) [6].
• In addition, improper creation of a new cysteine in Ang2 (Ang2S263C) dramatically induced Ang2 aggregation without activating Tie2 [13].
• Tie2 was tyrosine phoshorylated by Ang2 [9].
• 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 [14].

Other interactions of Ang2

• In the present study, the relationship of Angrp to Ang has been investigated by producing both proteins in bacteria and comparing their functional properties [15].
• Double-labeled immunostaining demonstrated that ZO-1-positive staining was significantly decreased on the microvessel wall in the VEGF plus Ang-2-treated group [16].
• Furthermore, the combination of VEGF and Ang-2 may lead to BBB disruption because it increases MMP-9 activity and inhibits ZO-1 expression [16].
• However, the function of angiopoietin-2 (Ang-2) in cerebral angiogenesis has not been clarified [16].
• Pigment epithelium-derived factor (PEDF) was increased more than 67-fold compared to Ang-2 in resting cornea of both C57BL/6J and 129S3/SvIM strains (P < 0.0001; P < 0.0001), suggesting a strongly antiangiogenic environment [17].

Analytical, diagnostic and therapeutic context of Ang2

• The fine structure of lymphatic capillaries in the digestive organs of angiopoietin-2 (Ang2) knockout mice was studied by using both immunohistochemistry and electron microscopy [11].
• After treatment with doxycycline to induce Ang2 expression, intravitreous injection of AGV.VEGF caused retinal neovascularization in addition to corneal and iris neovascularization [4].
• Examination of Ang2-treated xenografts revealed areas of tumor necrosis and vascular damage [18].
• In this study, for the first time, we investigated about the localization of VEGF-A, VEGFR-2 and Ang-2 in the choroid plexuses of the adult mouse by Western blot and immunohistochemistry [19].
• No significant effect was observed after intravitreal application of sTie2 (p = 0.07), although Ang-2 was upregulated in control animals without treatment as neovascularization developed and Ang-1 was constantly transcribed (ratio PCR) [20].

References