VEGF is essential for hypoxia-inducible factor-mediated neovascularization but dispensable for endothelial sprouting

Although our understanding of the molecular regulation of adult neovascularization has advanced tremendously, vascular-targeted therapies for tissue ischemia remain suboptimal. The master regulatory transcription factors of the hypoxia-inducible factor (HIF) family are attractive therapeutic targets because they coordinately up-regulate multiple genes controlling neovascularization. Here, we used an inducible model of epithelial HIF-1 activation, the TetON-HIF-1 mouse, to test the requirement for VEGF in HIF-1 mediated neovascularization. TetON-HIF-1, K14-Cre, and VEGF^(flox/flox) alleles were combined to create TetON-HIF-1:VEGFΔ mice to activate HIF-1 and its target genes in adult basal keratinocytes in the absence of concomitant VEGF. HIF-1 induction failed to produce neovascularization in TetON-HIF-1:VEGFΔ mice despite robust up-regulation of multiple proangiogenic HIF targets, including PlGF, adrenomedullin, angiogenin, and PAI-1. In contrast, endothelial sprouting was preserved, enhanced, and more persistent, consistent with marked reduction in Dll4-Notch-1 signaling. Optical-resolution photoacoustic microscopy, which provides noninvasive, label-free, high resolution, and wide-field vascular imaging, revealed the absence of both capillary expansion and arteriovenous remodeling in serially imaged individual TetON-HIF-1:VEGFΔ mice. Impaired TetON-HIF-1:VEGFΔ neovascularization could be partially rescued by 12-O-tetradecanoylphorbol-13-acetate skin treatment. These data suggest that therapeutic angiogenesis for ischemic cardiovascular disease may require treatment with both HIF-1 and VEGF

Optical-resolution photoacoustic microscopy of angiogenesis in a transgenic mouse model

A major obstacle in studying angiogenesis is the inability to noninvasively image neovascular development in an individual animal. We applied optical-resolution photoacoustic microscopy (OR-PAM) to determine the kinetics of hypoxia-inducible factor-1 (HIF-1)-mediated angiogenesis in a transgenic mouse model. During continuous 30-day activation of HIF-1α, we used OR-PAM to monitor alterations in microvasculature in transgenic mice compared to nontransgenic mice. OR-PAM has demonstrated the potential to precisely monitor antiangiogenic therapy of human cancers, allowing for rapid determinations of therapeutic efficacy or resistance

Texture Analysis and Radial Basis Function Approximation for IVUS Image Segmentation

>Intravascular ultrasound (IVUS) has become in the last years an important tool in both clinical and research applications. The detection of lumen and media-adventitia borders in IVUS images represents a first necessary step in the utilization of the IVUS data for the 3D reconstruction of human coronary arteries and the reliable quantitative assessment of the atherosclerotic lesions. To serve this goal, a fully automated technique for the detection of lumen and media-adventitia boundaries has been developed. This comprises two different steps for contour initialization, one for each corresponding contour of interest, based on the results of texture analysis, and a procedure for approximating the initialization results with smooth continuous curves. A multilevel Discrete Wavelet Frames decomposition is used for texture analysis, whereas Radial Basis Function approximation is employed for producing smooth contours. The proposed method shows promising results compared to a previous approach for texture-based IVUS image analysis

VEGF is essential for hypoxia-inducible factor-mediated neovascularization but dispensable for endothelial sprouting

Although our understanding of the molecular regulation of adult neovascularization has advanced tremendously, vascular-targeted therapies for tissue ischemia remain suboptimal. The master regulatory transcription factors of the hypoxia-inducible factor (HIF) family are attractive therapeutic targets because they coordinately up-regulate multiple genes controlling neovascularization. Here, we used an inducible model of epithelial HIF-1 activation, the TetON-HIF-1 mouse, to test the requirement for VEGF in HIF-1 mediated neovascularization. TetON-HIF-1, K14-Cre, and VEGF^(flox/flox) alleles were combined to create TetON-HIF-1:VEGFΔ mice to activate HIF-1 and its target genes in adult basal keratinocytes in the absence of concomitant VEGF. HIF-1 induction failed to produce neovascularization in TetON-HIF-1:VEGFΔ mice despite robust up-regulation of multiple proangiogenic HIF targets, including PlGF, adrenomedullin, angiogenin, and PAI-1. In contrast, endothelial sprouting was preserved, enhanced, and more persistent, consistent with marked reduction in Dll4-Notch-1 signaling. Optical-resolution photoacoustic microscopy, which provides noninvasive, label-free, high resolution, and wide-field vascular imaging, revealed the absence of both capillary expansion and arteriovenous remodeling in serially imaged individual TetON-HIF-1:VEGFΔ mice. Impaired TetON-HIF-1:VEGFΔ neovascularization could be partially rescued by 12-O-tetradecanoylphorbol-13-acetate skin treatment. These data suggest that therapeutic angiogenesis for ischemic cardiovascular disease may require treatment with both HIF-1 and VEGF

Substantiation of optical criterions of thermal-oxidative stability of lubricating oil

Research results of criteria of thermal-oxidative stability determined by different combinations of coefficient of absorption of light quantity and optical density with coefficient of evaporation and kinematic viscosity of oxygenated oil are presented. It is shown that the amount of optical density and the coefficient of evaporation divided by coefficient of relative viscosity are the most effective criteria of thermal-oxidative stability of lubricating oils de- scribed by second order polynomial with a high correlation coefficient

Molecular markers linked to papaya ring spot virus resistance and Fusarium race 2 resistance in melon

von Hauptman Heinrich Peÿer verfertiget ; F. Meyer sculpsitTitelkartusche oben links, Massstabsleisten unten rechtsWidmung unten rechts: "Denen hochgeachten ... Herren Burgermeistern und Rath lobl. Statt Schaffhausen zu sonderbahre Ehren in grund gelegt von Hauptman Heinrich Peyer verfertiget 1685