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CK Chan, C Chinn, C Spee, SJ Ryan, DR Hinton; Quiescent Endothelium is a Determinant of Strain-Dependent Angiogenesis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1758.
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Purpose: Angiogenesis, the growth of new vessels from pre-existing ones, is multi-step event that can be triggered by a variety of cytokines and growth factors. However, once initiated, the extent of new vessel growth is for the most part highly unpredictable. Recent experiments have shown that angiogenic potential, the extent of angiogenesis elicited by a particular stimulus, correlates with specific genetic backgrounds using a mouse model of bFGF-induced corneal angiogenesis. Since new vessel growth has been found to be associated with genetic factors, quiescent endothelium, the resting vasculature prior to any angiogenic stimulus, may also be modulated by similar factors. Methods: Using endothelial specific FITC-Griffonia simplicifolia lectin I -B4, corneal limbic vessel volume was determined for four inbred, weight- and age-matched mouse strains (c56BL/6, Balb/cJ, 129s3/Sv, and F1=c57BL/6 X 129s3/Sv) and quantified by 3-dimensional reconstruction confocal microscopy. Limbic vessel density was determined by summing the number of primary and secondary vessel branch points in 3 random fields of view. Results: Quiescent limbic vessel volume in 129s3/Sv, F1, and Balb/cJ strains resulted in over 8, 4, and 2 fold increases compared to c57BL/6 respectively (p<0.05). Limbic vessel density also resulted in a similar strain-dependent trend: c57BL/6 < Balb/cJ, F1 < 129s3/Sv; (p<0.05). This strain-dependent trend in quiescent vascular volume and vascular density parallels trends previously reported (and reproduced in our laboratory) for bFGF-induced corneal angiogenesis. Conclusion: This data suggests that genetic factors determining quiescent vascularity established during vasculogenesis may in part dictate adult angiogenesis. Subsequently, quiescent endothelium may determine the severity of angiogenesis-dependent diseases. Furthermore, elucidation and modulation of genetic factors influencing the quiescent vasculature may provide effective therapy toward angiogenesis-dependent diseases.
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