Opioid growth factor modulates angiogenesis

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Presentation transcript:

Opioid growth factor modulates angiogenesis John Blebea, MDa, James E. Mazo, MDa, Todd K. Kihara, MDa, Jonathan-Hien Vu, MDa, Patricia J. McLaughlin, DEdb, Robert G. Atnip, MDa, Ian S. Zagon, PhDb Journal of Vascular Surgery Volume 32, Issue 2, Pages 364-373 (August 2000) DOI: 10.1067/mva.2000.107763b Copyright © 2000 Society for Vascular Surgery and The American Association for Vascular Surgery, a Chapter of the International Society for Cardiovascular Surgery Terms and Conditions

Fig. 1 Digitized computer images of 7-day-old CAMs. In contrast to control specimens (A), CAMs treated with retinoic acid (B) exhibited marked decrease in blood vessel growth in 100-mm2 region around disk. After treatment with OGF (C), blood vessel growth is suppressed in comparison with control samples. Vessel inhibition is no longer seen after treatment with naltrexone (D). Note circle representing applied disk (cross-hatched arrow) and surrounding blood vessels (arrow). Bar = 5 mm. Journal of Vascular Surgery 2000 32, 364-373DOI: (10.1067/mva.2000.107763b) Copyright © 2000 Society for Vascular Surgery and The American Association for Vascular Surgery, a Chapter of the International Society for Cardiovascular Surgery Terms and Conditions

Fig. 2 Comparison of total numbers of blood vessels in region around applied disks. Number of blood vessels is significantly decreased in OGF group and increased in naltrexone group in comparison with control preparations. Significant differences from controls: *P <.005; #P <.001. Journal of Vascular Surgery 2000 32, 364-373DOI: (10.1067/mva.2000.107763b) Copyright © 2000 Society for Vascular Surgery and The American Association for Vascular Surgery, a Chapter of the International Society for Cardiovascular Surgery Terms and Conditions

Fig. 3 Total blood vessel length is significantly inhibited in CAMs exposed to OGF and increased after treatment with naltrexone. Simultaneous treatment with naloxone prevented inhibition by OGF. Significant difference from controls: *P <.005. Journal of Vascular Surgery 2000 32, 364-373DOI: (10.1067/mva.2000.107763b) Copyright © 2000 Society for Vascular Surgery and The American Association for Vascular Surgery, a Chapter of the International Society for Cardiovascular Surgery Terms and Conditions

Fig. 4 Mean blood vessel length is significantly increased by treatment with OGF, whereas naltrexone decreased mean blood vessel length. Significant differences from controls: #P <.001; †P <.0005. Journal of Vascular Surgery 2000 32, 364-373DOI: (10.1067/mva.2000.107763b) Copyright © 2000 Society for Vascular Surgery and The American Association for Vascular Surgery, a Chapter of the International Society for Cardiovascular Surgery Terms and Conditions

Fig. 5 Immunocytochemical preparation of isolated principal CAM vessels. Cross section of vessel stained with hematoxylin-eosin shows its morphologic structure at this early developmental stage, with flattened inner endothelial cells (arrows) and mesenchymal presumptive immature smooth muscle cells (curved arrow)(A). Sections of vessels have been incubated with antibodies to OGF (B, C) or OGF receptor (D, E) at 1:100 dilutions. Note staining of cytoplasm (arrowheads) of cells throughout wall of vessels and nonstaining of nuclei. Fig 5, C and E shows control sections stained with antibodies to OGF and OGF receptor, respectively, after preabsorption with excess OGF and OGF receptor; they did not exhibit any immunofluorescence. Times of exposure and printing correspond in all photos. Bar = 48 μm for Fig 5, A and 16 μm for Fig 5, B-E. Journal of Vascular Surgery 2000 32, 364-373DOI: (10.1067/mva.2000.107763b) Copyright © 2000 Society for Vascular Surgery and The American Association for Vascular Surgery, a Chapter of the International Society for Cardiovascular Surgery Terms and Conditions

Fig. 6 In another series of experiments, angiogenic inhibitor retinoic acid has significantly diminished number of blood vessels, whereas VEGF markedly increased angiogenesis (§P <.0001). Journal of Vascular Surgery 2000 32, 364-373DOI: (10.1067/mva.2000.107763b) Copyright © 2000 Society for Vascular Surgery and The American Association for Vascular Surgery, a Chapter of the International Society for Cardiovascular Surgery Terms and Conditions

Fig. 7 Retinoic acid decreased total length of measured blood vessels whereas VEGF induced marked increase in comparison with controls (§P <.0001). Journal of Vascular Surgery 2000 32, 364-373DOI: (10.1067/mva.2000.107763b) Copyright © 2000 Society for Vascular Surgery and The American Association for Vascular Surgery, a Chapter of the International Society for Cardiovascular Surgery Terms and Conditions

Fig. 8 Inhibition of new vessel development by retinoic acid increased calculated mean vessel length, whereas VEGF is associated with decreased values in comparison with control preparations (§P <.0001). Journal of Vascular Surgery 2000 32, 364-373DOI: (10.1067/mva.2000.107763b) Copyright © 2000 Society for Vascular Surgery and The American Association for Vascular Surgery, a Chapter of the International Society for Cardiovascular Surgery Terms and Conditions