Clin Res Cardiol 101, Suppl 1, April 2012

P367 - Nucleoside diphosphate kinase B deficiency protects from pathological hypoxia-induced retinal angiogenesis
Y. Feng1, V. M. Butenschön1, Y. Qiu1, H.-P. Hammes2, E. Y. Skolnik3, T. Wieland1
1Institut für Experimentelle u. Klinische Pharmakologie und Toxikologie, Universität Heidelberg, Mannheim; 2Med V. - Nephrologie, Endokrinologie und Rheumatologie, Universitätsmedizin Mannheim, Mannheim; 3Division of Nephrology, New York University Langone Medical Center, New York, USA;
Aim: Nucleoside diphosphate kinase B (NDPK B) activates G Proteins in a receptor-independent manner. Our previous data showed that NDPK B knockdown exerts an anti-angiogenic effect in the vascular development of the zebrafish. In this study we therefore ought to investigate the role of NDPK B in a hypoxia-induced retinal angiogenesis model (OIR) using NDPK B knockout mice.
Methods: NDPK B knockout mice (KO) and wildtype (WT) littermates with C57Bl background were used for the study. Firstly, we analyzed the physiological angiogenesis of the mice at postnatal day (p) 5 and p10. The whole mount retinal vasculature was stained either with FITC labeled isolectin or antibodies against collagen IV. The superficial and deep capillary layers were quantified and expressed in absolute areas at p5 or in ratio of deep to superficial layer at p10. Subsequently, the mice were examined in OIR. New born mice were subjected to 75% oxygen with their nursing mother at p7. At p12 they returned to room air and were held for additional 5 days up to p17. The expression of NDPK B under hypoxia was assessed in the whole mount retina from WT mice at p14 with a specific NDPK B antibody. Furthermore, the angiogenic response in the retina of WT and KO mice was compared at p17 by counting neovascular nuclei penetrating the inner limiting membrane.
Results: There was no difference in physiological retinal angiogenesis between the KO mice and their WT littermates at p5 and p10 in the superficial as well the deep capillary layers. NDPK B was expressed weakly in endothelial cells, smooth muscle cells and pericytes in the normal retina. Interestingly, NDPK B expression was strongly increases under hypoxia in the OIR model in retinal arterioles and neovascularizations in the smooth muscle cells and pericytes. Importantly, the amount of hypoxia-induced pre-retinal neovascularizations was significantly reduced in the OIR model at p17 by about 70%. There was no difference in the morphology of retinal arterioles, venules and capillaries between NDPK B knockout and control mice.
Conclusions: Our data demonstrate that the retinal vascular development in physiological condition is not effected by the NDPK B deficiency. However, the NDPK B expressed in the smooth muscle cells and pericytes is required for the angiogenic response of the retinal vessels under hypoxia. The strong reduction of the pathophysiological angiogenesis in the retina of KO mice indicates that the inhibition of NDPK B activity or the suppression of its upregulation may be beneficial for some diseases with excessive vessel growth.
Clin Res Cardiol 101, Suppl 1, April 2012
Zitierung mit Vortrags- oder Posternummer s.o.
DOI 10.1007/s00392-012-1100-6