Disease relevance of Ang1

• However, when Ang1 expression was initiated simultaneously with that of VEGF, it strongly suppressed VEGF-induced NV and prevented retinal detachment [1].
• The contribution of COMP-Ang1 in renal interstitial fibrosis, however, remains to be clarified [2].
• This study investigated the effects of COMP-Ang1 on peritubular capillary EC in the renal cortex and the renal fibrogenic process that is triggered by unilateral ureteral obstruction [2].
• These observations demonstrate the potential of Ang1 as a new therapeutic modality for MC dropout in diseases such as diabetic retinopathies [3].
• Increased expression of Ang1 in eyes with severe retinal ischemia or in eyes with rupture of Bruch's membrane significantly suppressed the development of retinal or choroidal neovascularization, respectively [4].

High impact information on Ang1

• The angiopoietins Ang-1 and Ang-2 have been identified as ligands of the receptor tyrosine kinase Tie-2 (refs. 1,2) [5].
• Direct comparison of transgenic mice overexpressing these factors in the skin revealed that the VEGF-induced blood vessels were leaky, whereas those induced by Ang1 were nonleaky [6].
• Finally, ephrinB ligands induce capillary sprouting in vitro with a similar efficiency as angiopoietin-1 (Ang1) and vascular endothelial growth factor (VEGF), demonstrating a stimulatory role of ephrins in the remodeling of the developing vascular system [7].
• In Langendorff-perfused guinea pig hearts, mast cell degranulation with compound 48/80 released Ang I-forming activity [8].
• Taken together, these findings indicate that COMP-Ang1 can promote wound healing in diabetes through enhanced angiogenesis, lymphangiogenesis, and blood flow [9].

Chemical compound and disease context of Ang1

• Because endotoxin-induced shock is a condition with microvascular leakage resulting from inflammation, we examined the potential therapeutic benefit of Ang1 in a murine model of lipopolysaccharide (LPS)-induced endotoxic shock [10].
• Our group has shown previously that RV inhibits angiotensin II (Ang II)-induced Akt activation and, consequently, vascular smooth muscle cell (VSMC) hypertrophy [11].
• The highly lipophilic ACE inhibitor imidapril (Vitortrade mark) (30 mg kg(-1)) attenuated the development of weight loss in mice bearing the MAC16 tumour, suggesting that Ang II may play a role in the development of cachexia in this model [12].
• 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 [13].

Biological context of Ang1

• We observed that hepatocyte growth factor (HGF), a mediator of mural cell motility, was up-regulated by Ang1 stimulation [14].
• Ang2 is known to inhibit Ang1-mediated phosphorylation of Tie2 as well as cellular responses during embryonic development [15].
• Unexpectedly, screening of a genomic library with an Ang gene probe obtained previously from the BALB/c strain yielded two new genes closely similar to Ang rather than Ang itself [16].
• Renal surface microvasculature and renal blood flow were higher after treatment with COMP-Ang1 than with vehicle [2].
• Conserved among humans, mice and rats, the locus includes two non-coding exons followed by two distinct exons encoding RNase 4 and RNase 5/ang 1 [17].

Anatomical context of Ang1

• Furthermore, stimulation of ECs with Ang1 increased SMC migration toward endothelial cells in a coculture assay [14].
• In this study, murine macrophages constitutively expressed both transcripts and protein for Ang2 but not Ang1 or Ang3 [18].
• The genetic replacement of Ang2 with Ang1 rescued the defects, viz., the disorganization and disordered structure of the lymphatic capillaries [19].
• These results reinforce the role of ACTH in the regulation of angiogenic factors in adrenal gland and suggest that the Ang/Tie2 system might represent a key player for stabilization of adrenal endothelium [20].
• Adult mice with induced expression of Ang1 ubiquitously, or specifically in the retina, appeared normal and had no identifiable changes in retinal or choroidal blood vessels or in retinal function as assessed by electroretinography [4].

Associations of Ang1 with chemical compounds

• This study investigated the expression patterns of the Ang-Tie-2 family of endothelium-specific receptor tyrosine kinases and vascular endothelial growth factors and their receptors (VEGF-VEGFR system) during postnatal mouse lung development [21].
• The Ang1-induced ROS was identified as hydrogen peroxide (H2O2) using adenovirus-catalase infection [22].
• 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 [22].
• After intraperitoneal glucose challenge, COMP-Ang1 significantly lowered plasma glucose levels [23].
• 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 [24].

Other interactions of Ang1

• In the present study, the relationship of Angrp to Ang has been investigated by producing both proteins in bacteria and comparing their functional properties [25].
• This and other evidence suggests that the RNase A superfamily originated from an RNase 5-like gene and expanded in mammals [26].
• A chimeric mouse/human antibody directed against the human transferrin receptor (E6) was fused at its CH2 domain to the gene for a human angiogenic ribonuclease, angiogenin (Ang) [27].
• The enhanced survival rate induced by Ang1 was accompanied by an improvement in hemodynamic function, reduced lung injury, a lower expression of inflammatory adhesion molecules, and preserved eNOS activity in the lung tissue [10].

Analytical, diagnostic and therapeutic context of Ang1

• Although the Ang gene was not isolated from this library, it was possible to amplify this gene from 129 mouse genomic DNA by the polymerase chain reaction (PCR) [16].
• Sequence analysis showed that the 129 strain Ang gene is identical to the BALB/c gene throughout the coding region [16].
• Using semiquantitative RT-PCR, we demonstrate that DEX treatment down regulates Ang-1 mRNA levels by 3- to 4-fold [20].
• We previously reported that overexpression of Ang1 in MCF7 xenograft tumors facilitated vessel stabilization by mural cells, and that cultured SMC express Tie2 [28].
• Intravenous injection of adenovirus encoding VEGF (Adeno-VEGF) resulted in widespread tissue oedema within 1-2 days after administration, whereas injection of Adeno-Ang1 resulted in the skin vessels becoming less leaky in response to topical inflammatory stimuli or local injection of VEGF [29].

References