Analysis Tools
cardiovascular system
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• despite accelerated retinal angiogenesis, mutant mice have normal pericyte coverage in both front and central regions of the vascular plexus in P5 retinas, and show no evidence of retinal vascular leakage at 10 months of age
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• at P3-P5, mutant mice exhibit accelerated retinal angiogenesis, as shown by a greater radial extension of the vascular plexus from the optic nerve to the periphery, an increased number of branch points in both front and central areas of the vascular plexus, and a higher number of endothelial tip cells as well as filopodia relative to control mice
• accelerated retinal angiogenesis is associated with attenuated Notch signaling, as shown by decreased NICD (Notch intracellular domain) protein levels, reduced Hey1, Hey2, and Hes1 mRNA levels, and increased VEGFR2 activation
• following treatment with DAPT (a Notch inhibitor) at P4, retinal angiogenesis is inhibited to a significantly lesser degree than in control mice at P5
• notably, untreated retinas show normal vascular remodeling with no apparent change in the number of ColIV+CD31 empty sleeves at P5, and no differences in blood vessel formation at P7 and P9
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• in a s.c. Matrigel plug assay that mimics ischemic/inflammatory neovascularization, plugs retrieved from mutant mice exhibit significantly more neovessel formation than plugs from control mice
• enhanced pathological angiogenesis in Matrigel plugs is associated with attenuated Notch activity, as shown by decreased NICD protein levels and reduced Hey1, Hey2, and Hes1 mRNA levels
• in a murine hindlimb ischemia model, mutant mice show a significant increase in gastrocnemius capillary density and enhanced recovery of limb perfusion relative to control mice
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