Endothelium-specific deletion of Nox4 delays retinal vascular development and mitigates pathological angiogenesis.

Angiogenesis
Xixiang TangSarah X Zhang

Abstract

NADPH oxidase 4 (Nox4) is a major isoform of NADPH oxidases playing an important role in many biological processes. Previously we have shown that Nox4 is highly expressed in retinal blood vessels and is upregulated in oxygen-induced retinopathy (OIR). However, the exact role of endothelial Nox4 in retinal angiogenesis remains elusive. Herein, using endothelial cell (EC)-specific Nox4 knockout (Nox4EC-KO) mice, we investigated the impact of endothelial Nox4 deletion on retinal vascular development and pathological angiogenesis during OIR. Our results show that deletion of Nox4 in ECs led to retarded retinal vasculature development with fewer, blunted-end tip cells and sparser, dysmorphic filopodia at vascular front, and reduced density of vascular network in superficial, deep, and intermediate layers in postnatal day 7 (P7), P12, and P17 retinas, respectively. In OIR, loss of endothelial Nox4 had no effect on hyperoxia-induced retinal vaso-obliteration at P9 but significantly reduced aberrant retinal neovascularization at P17 and decreased the deep layer capillary density at P25. Ex vivo study confirmed that lack of Nox4 in ECs impaired vascular sprouting. Mechanistically, loss of Nox4 significantly reduced expression of VEGF, p...Continue Reading

References

May 11, 2001·The Journal of Biological Chemistry·T R CarlsonA O Morla
Jul 13, 2002·Journal of Cellular Physiology·Sean F HackettPeter A Campochiaro
Jun 18, 2003·The Journal of Cell Biology·Holger GerhardtChrister Betsholtz
Sep 2, 2005·The Journal of Biological Chemistry·Yves GorinHanna E Abboud
Dec 24, 2005·American Journal of Physiology. Cell Physiology·Helena ParfenovaCharles W Leffler
Jun 17, 2006·Cancer Research·Young Mee KimKong-Joo Lee
Jun 2, 2007·Circulation Research·Yvonne ReissKarl H Plate
Apr 15, 2008·Cancer Letters·Masuko Ushio-Fukai, Yoshimasa Nakamura
Jul 29, 2008·Microvascular Research·Michiyo Kobayashi-SakamotoItsuo Chiba
Sep 12, 2008·Antioxidants & Redox Signaling·Srikanth PendyalaViswanathan Natarajan
Feb 24, 2009·Nature Reviews. Molecular Cell Biology·Hellmut G AugustinKari Alitalo
Apr 2, 2009·Naunyn-Schmiedeberg's Archives of Pharmacology·Hitesh PeshavariyaStavros Selemidis
Jul 22, 2009·The Journal of Clinical Investigation·Sulochana S BhandarkarJack L Arbiser
May 21, 2010·Investigative Ophthalmology & Visual Science·Andreas StahlLois E H Smith
Sep 28, 2010·Nature Cell Biology·Lars JakobssonHolger Gerhardt
Apr 14, 2011·Current Cancer Drug Targets·P Sapra SharmaT Tyagi
May 20, 2011·Nature·Peter Carmeliet, Rakesh K Jain
Oct 4, 2011·Development·Ilse Geudens, Holger Gerhardt
Nov 24, 2011·PloS One·Enrique ZudaireSonja Vermeren
May 16, 2012·The Journal of Clinical Investigation·Moritz FelchtHellmut G Augustin
Oct 23, 2012·Cold Spring Harbor Perspectives in Medicine·Raquel Blanco, Holger Gerhardt
Feb 11, 2014·Methods in Molecular Biology·Jennifer V Welser-AlvesRichard Milner
Jul 26, 2014·Biochemistry·Yukio NisimotoJ David Lambeth
Jul 30, 2014·Trends in Endocrinology and Metabolism : TEM·Grant R Drummond, Christopher G Sobey
Dec 10, 2014·Journal of Visualized Experiments : JoVE·Tobias RuckSven G Meuth
Jan 31, 2015·Nature Communications·Laura HakanpaaPipsa Saharinen
Feb 6, 2015·The Journal of Physiology·Juri VogelKatrin Schröder
Dec 20, 2016·Annual Review of Physiology·Michael Potente, Peter Carmeliet

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Apr 1, 2021·Free Radical Biology & Medicine·Gesine WackWiebke Kallenborn-Gerhardt

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