TY - JOUR
T1 - Nox4 supports proper capillary growth in exercise and retina neo-vascularization
AU - Vogel, Juri
AU - Kruse, Christoph
AU - Zhang, Min
AU - Schröder, Katrin
PY - 2015/5/11
Y1 - 2015/5/11
N2 - By producing H2O2, the NADPH oxidase Nox4 is involved in hypoxia-induced angiogenesis, as present in vascular remodelling of the hypertrophic heart or blood flow recovery after hind limb ischaemia. In the present study, we hypothesized that Nox4 contributes to proper capillary growth in the retina and in exercised muscles and investigated this in wild-type and Nox4-/- mice. Exercise, as induced by voluntary running in a running wheel or forced running on a treadmill, stimulated capillary growth in wild-type but not Nox4-/- mice. As an underlying mechanism, we identified both vascular endothelial growth factor (VEGF) expression to be reduced and angiopoietin 1 (Ang1) expression to be increased in response to Nox4 knockout. To differentiate the two factors, oxygen-induced retinopathy was investigated. In this model, deletion of Nox4 protected from neo-angiogenesis and stabilized the network of regrown vessels, which is a typical feature of Ang1. However the angiogenesis in the developing retina was similar between Nox4-/- and wild-type mice. Thus, Nox4 contributes to exercise- and hypoxia-induced angiogenesis through a dual mechanism of maintaining VEGF and preventing Ang-1 expression, whereas the developmental angiogenesis is Nox4 independent.
AB - By producing H2O2, the NADPH oxidase Nox4 is involved in hypoxia-induced angiogenesis, as present in vascular remodelling of the hypertrophic heart or blood flow recovery after hind limb ischaemia. In the present study, we hypothesized that Nox4 contributes to proper capillary growth in the retina and in exercised muscles and investigated this in wild-type and Nox4-/- mice. Exercise, as induced by voluntary running in a running wheel or forced running on a treadmill, stimulated capillary growth in wild-type but not Nox4-/- mice. As an underlying mechanism, we identified both vascular endothelial growth factor (VEGF) expression to be reduced and angiopoietin 1 (Ang1) expression to be increased in response to Nox4 knockout. To differentiate the two factors, oxygen-induced retinopathy was investigated. In this model, deletion of Nox4 protected from neo-angiogenesis and stabilized the network of regrown vessels, which is a typical feature of Ang1. However the angiogenesis in the developing retina was similar between Nox4-/- and wild-type mice. Thus, Nox4 contributes to exercise- and hypoxia-induced angiogenesis through a dual mechanism of maintaining VEGF and preventing Ang-1 expression, whereas the developmental angiogenesis is Nox4 independent.
UR - http://www.scopus.com/inward/record.url?scp=84928826769&partnerID=8YFLogxK
U2 - 10.1113/jphysiol.2014.284901
DO - 10.1113/jphysiol.2014.284901
M3 - Article
C2 - 25652847
AN - SCOPUS:84928826769
SN - 0022-3751
VL - 593
SP - 2145
EP - 2154
JO - The Journal of Physiology
JF - The Journal of Physiology
IS - 9
ER -