Feng, Yuxi; Wang, Yumei; Pfister, Frederick; Hillebrands, Jan-Luuk; Deutsch, Urban; Hammes, Hans-Peter (2009). Decreased hypoxia-induced neovascularization in angiopoietin-2 heterozygous knockout mouse through reduced MMP activity. Cellular physiology and biochemistry, 23(4-6), pp. 277-84. Basel: Karger 10.1159/000218174
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BACKGROUND/AIMS: Proliferative diabetic retinopathy is characterized by the formation of retinal neovascularization. Angiopoietin-2 (Ang-2) and matrix metalloproteinase (MMP) play a critical role in angiogenesis. However, the precise location and function of Ang-2 during formation of retinal neovascularizations driven by hypoxia in relation to MMP activity have not been elucidated. In this study, we investigated the response of Ang-2 heterozygous knockout retinas (Ang2(+/-) mouse) to hypoxia and its link to MMP activity in an oxygen-induced retinopathy (OIR) model. METHODS: Pre-retinal neovascularizations were quantitated in vertical sections. Intra-retinal angiogenesis was assessed by whole mount immunofluorescence staining of retinas. MMP activity was examined in retinal protein lysate and whole mount retinal in situ zymography. RESULTS: Ang2(+/-) retinas subjected to the OIR model showed 33% reduced neovascularization and 271% increased avascular zones at postnatal day 17. In the OIR model, Ang-2 was modestly expressed in pre-retinal neovascularizations and venules, but strongly in arterioles and capillary sprouts. MMPs were activated in close association to where Ang-2 is expressed. MMP activity was substantially decreased in Ang2(+/-) retinas. CONCLUSIONS: Our present data suggest the spatially concomitant expression of Ang2 and MMPs, and that Ang2 modulates hypoxia-induced neovascularization by regulating MMP activity.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Deutsch, Urban |
ISSN: |
1015-8987 |
Publisher: |
Karger |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:13 |
Last Modified: |
25 May 2023 15:01 |
Publisher DOI: |
10.1159/000218174 |
PubMed ID: |
19471095 |
Web of Science ID: |
000265864700006 |
BORIS DOI: |
10.48350/32150 |
URI: |
https://boris.unibe.ch/id/eprint/32150 (FactScience: 197078) |
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