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Functional Role of Mural Cell NG2 in Angiogenesis and Vasculogenesis

, : Functional Role of Mural Cell NG2 in Angiogenesis and Vasculogenesis. ARVO Annual Meeting Abstract Search & Program Planner : Abstract No 1327

Purpose: Several in vivo mouse models have been used to investigate the functional role of the NG2 proteoglycan in normal and pathological neovascularization. Methods: In addition to developmental neovascularization (from ages E5-P11), pathological neovascularization was studied in two eye models: bFGF-induced corneal angiogenesis (at post-operative days 3-28) and hyperoxia-induced retinal angiogenesis (at age P17). Using the Bio-Rad MRC-1024MP confocal microscope, a survey of NG2 expression was made by comparison of immunofluorecence double staining with endothelial (CD31, flk1, CD105) and mural cell (alpha-SMA, PDGF beta-receptor) markers. Morphometric comparisons between the vasculature of wild-type and NG2-null mice were made using both serial histological sections and polymer casts of the entire vascular tree. Results: NG2 is expressed exclusively by the mural cell component in all types of vasculature. During embryonic and postnatal vascular morphogenesis and in both pathological models, NG2-positive pericytes are associated with endothelial tubes and angiogenic sprouts at an early time point during microvascular development. A role for NG2 in this early relationship between vascular endothelial and mural cells is indicated in the retinal hyperoxia model by a 54.1% decrease (p=0.0019) in the neovascularization seen in histological sections from the NG2-null mouse. During normal development of the NG2-null retina, secondary and tertiary vascular plexi fail to develop on schedule by P11 from the primary plexus. The absence of NG2 also affects macrovascular development. At E10 the NG2-null heart is distinguished from the wild-type heart by ventricular enlargement and by a smaller diameter, thinner-walled outflow tract. Polymer casts prepared from postnatal NG2 null mice suggest the presence of a ventricular septal defect. Conclusion: Use of NG2 as a mural cell marker has allowed the observation of a close and early relationship between pericytes and endothelial cells in developing microvessels. A functional role for NG2 in communication between these two cell types is indicated by the finding of diminished angiogenesis in NG2-null mice. A similar role for NG2 in vasculogenesis is suggested by macrovascular changes in NG2 knockout animals.


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