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S. Nakamura, H. Izuta, K. Tsuruma, M. Shimazawa, H. Hara; Effects of Kallidinogenase on Retinal Neovasocularization. Invest. Ophthalmol. Vis. Sci. 2009;50(13):50.
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Kallidinogenase is widely used as a vasodilator in the treatments of hypertention and peripheral circulatory disorder. Recently, it has been reported that kallidinogenase reduces intraocular vascular endothelial growth factor (VEGF) level, associated with angiogenesis, in streptozotocin-induced diabetic rats. Therefore, we examined whether kallidinogenase has anti-angiogenic effects in vitro and in vivo models.
Human umbilical vein endothelial cells (HUVECs) were co-cultured with human fibroblasts and incubated for 11 days with or without kallidinogenase, with the concominant addition of VEGF(10 ng/ml). Tube formation was measured using an Angiogenesis Image Analyzer. Proliferation and migration of HUVECs were measured using the WST-8 assay and the wound-healing assay, respectively. Retinal neovasuclarization was induced in neonatal mice by returning the retina to normoxia (21% O2) after exposure to hyperoxia (75% O2) from postnatal day 7 (P7) to P12. Kallidinogenase was subcutaneously administered at 20 and 50 µg/kg once a day from immediately after hyperoxia to P16. At P17, flat-mounted retinas were prepared and evaluated for pathological and physiological angiogenesis.
Kallidinogenase significantly suppressed in vitro HUVEC tube formation, proliferation, and migration. Furthermore, kallidinogenase significantly suppressed in vivo retinal neovascularization (versus vehicle treatment), but revascularization of the capillary free area did not differ between vehicle and kallidinogenase treatments.
Kallidinogenase has anti-angiogenic effects in vitro and in vivo, and may be useful as an anti-angiogenic agent in the treatment of retinal neovascularization diseases.
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