Abstract
The endothelial and smooth muscle integrin alphaVbeta3, a receptor for vitronectin and fibrinogen, participates in angiogenesis associated with wound healing and tumorigenicity. The microvascular expression of alphavbeta3 and fibrin during experimental middle cerebral artery occlusion and reperfusion in a nonhuman primate model was examined by computer-assisted video imaging microscopy. No microvascular expression of alphavbeta3 was seen in the control subjects (n = 3) or the non-ischemic basal ganglia of subjects undergoing 2-hour MCA:O (middle cerebral artery occlusion) or 3-hour occlusion with 1-hour (n = 3), 4-hour (n = 3), and 24-hour (n = 3) reperfusion. In the ischemic territory, alphavbeta3 appeared initially at 2 hours of middle cerebral artery occlusion. Up-regulation of alphavbeta3 was confined to the media of 30.0- to 50.0-micron-diameter arterioles in the ischemic core and correlated significantly with fibrin deposition in those vessels (P < 0.0005). Integrin alphavbeta3 and its ligand fibrinogen appear in a subpopulation of microvessels after focal cerebral ischemia.
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- Brooks P. C., Clark R. A., Cheresh D. A. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994 Apr 22;264(5158):569–571. doi: 10.1126/science.7512751. [DOI] [PubMed] [Google Scholar]
- Brooks P. C., Montgomery A. M., Rosenfeld M., Reisfeld R. A., Hu T., Klier G., Cheresh D. A. Integrin alpha v beta 3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell. 1994 Dec 30;79(7):1157–1164. doi: 10.1016/0092-8674(94)90007-8. [DOI] [PubMed] [Google Scholar]
- Charo I. F., Nannizzi L., Smith J. W., Cheresh D. A. The vitronectin receptor alpha v beta 3 binds fibronectin and acts in concert with alpha 5 beta 1 in promoting cellular attachment and spreading on fibronectin. J Cell Biol. 1990 Dec;111(6 Pt 1):2795–2800. doi: 10.1083/jcb.111.6.2795. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheresh D. A. Human endothelial cells synthesize and express an Arg-Gly-Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6471–6475. doi: 10.1073/pnas.84.18.6471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheresh D. A., Smith J. W., Cooper H. M., Quaranta V. A novel vitronectin receptor integrin (alpha v beta x) is responsible for distinct adhesive properties of carcinoma cells. Cell. 1989 Apr 7;57(1):59–69. doi: 10.1016/0092-8674(89)90172-4. [DOI] [PubMed] [Google Scholar]
- Cheresh D. A., Spiro R. C. Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. J Biol Chem. 1987 Dec 25;262(36):17703–17711. [PubMed] [Google Scholar]
- Cheresh D. A. Structure, function and biological properties of integrin alpha v beta 3 on human melanoma cells. Cancer Metastasis Rev. 1991 May;10(1):3–10. doi: 10.1007/BF00046839. [DOI] [PubMed] [Google Scholar]
- Del Zoppo G. J., Copeland B. R., Harker L. A., Waltz T. A., Zyroff J., Hanson S. R., Battenberg E. Experimental acute thrombotic stroke in baboons. Stroke. 1986 Nov-Dec;17(6):1254–1265. doi: 10.1161/01.str.17.6.1254. [DOI] [PubMed] [Google Scholar]
- Eke A., Conger K. A., Anderson M., Garcia J. H. Histologic assessment of neurons in rat models of cerebral ischemia. Stroke. 1990 Feb;21(2):299–304. doi: 10.1161/01.str.21.2.299. [DOI] [PubMed] [Google Scholar]
- Freed E., Gailit J., van der Geer P., Ruoslahti E., Hunter T. A novel integrin beta subunit is associated with the vitronectin receptor alpha subunit (alpha v) in a human osteosarcoma cell line and is a substrate for protein kinase C. EMBO J. 1989 Oct;8(10):2955–2965. doi: 10.1002/j.1460-2075.1989.tb08445.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garcia J. H., Liu K. F., Yoshida Y., Lian J., Chen S., del Zoppo G. J. Influx of leukocytes and platelets in an evolving brain infarct (Wistar rat). Am J Pathol. 1994 Jan;144(1):188–199. [PMC free article] [PubMed] [Google Scholar]
- Giachelli C. M., Liaw L., Murry C. E., Schwartz S. M., Almeida M. Osteopontin expression in cardiovascular diseases. Ann N Y Acad Sci. 1995 Apr 21;760:109–126. doi: 10.1111/j.1749-6632.1995.tb44624.x. [DOI] [PubMed] [Google Scholar]
- Haring H. P., Akamine B. S., Habermann R., Koziol J. A., Del Zoppo G. J. Distribution of integrin-like immunoreactivity on primate brain microvasculature. J Neuropathol Exp Neurol. 1996 Feb;55(2):236–245. doi: 10.1097/00005072-199602000-00012. [DOI] [PubMed] [Google Scholar]
- Humphries M. J., Olden K., Yamada K. M. A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science. 1986 Jul 25;233(4762):467–470. doi: 10.1126/science.3726541. [DOI] [PubMed] [Google Scholar]
- Humphries M. J., Yamada K. M., Olden K. Investigation of the biological effects of anti-cell adhesive synthetic peptides that inhibit experimental metastasis of B16-F10 murine melanoma cells. J Clin Invest. 1988 Mar;81(3):782–790. doi: 10.1172/JCI113384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kramer R. H., Cheng Y. F., Clyman R. Human microvascular endothelial cells use beta 1 and beta 3 integrin receptor complexes to attach to laminin. J Cell Biol. 1990 Sep;111(3):1233–1243. doi: 10.1083/jcb.111.3.1233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lawler J., Weinstein R., Hynes R. O. Cell attachment to thrombospondin: the role of ARG-GLY-ASP, calcium, and integrin receptors. J Cell Biol. 1988 Dec;107(6 Pt 1):2351–2361. doi: 10.1083/jcb.107.6.2351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liaw L., Skinner M. P., Raines E. W., Ross R., Cheresh D. A., Schwartz S. M., Giachelli C. M. The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro. J Clin Invest. 1995 Feb;95(2):713–724. doi: 10.1172/JCI117718. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu T., Clark R. K., McDonnell P. C., Young P. R., White R. F., Barone F. C., Feuerstein G. Z. Tumor necrosis factor-alpha expression in ischemic neurons. Stroke. 1994 Jul;25(7):1481–1488. doi: 10.1161/01.str.25.7.1481. [DOI] [PubMed] [Google Scholar]
- Okada Y., Copeland B. R., Fitridge R., Koziol J. A., del Zoppo G. J. Fibrin contributes to microvascular obstructions and parenchymal changes during early focal cerebral ischemia and reperfusion. Stroke. 1994 Sep;25(9):1847–1854. doi: 10.1161/01.str.25.9.1847. [DOI] [PubMed] [Google Scholar]
- Reinholt F. P., Hultenby K., Oldberg A., Heinegård D. Osteopontin--a possible anchor of osteoclasts to bone. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4473–4475. doi: 10.1073/pnas.87.12.4473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Senger D. R., Perruzzi C. A., Papadopoulos-Sergiou A., Van de Water L. Adhesive properties of osteopontin: regulation by a naturally occurring thrombin-cleavage in close proximity to the GRGDS cell-binding domain. Mol Biol Cell. 1994 May;5(5):565–574. doi: 10.1091/mbc.5.5.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spetzler R. F., Selman W. R., Weinstein P., Townsend J., Mehdorn M., Telles D., Crumrine R. C., Macko R. Chronic reversible cerebral ischemia: evaluation of a new baboon model. Neurosurgery. 1980 Sep;7(3):257–261. doi: 10.1227/00006123-198009000-00009. [DOI] [PubMed] [Google Scholar]
- Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
- Thomas W. S., Mori E., Copeland B. R., Yu J. Q., Morrissey J. H., del Zoppo G. J. Tissue factor contributes to microvascular defects after focal cerebral ischemia. Stroke. 1993 Jun;24(6):847–847. doi: 10.1161/01.str.24.6.847. [DOI] [PubMed] [Google Scholar]
- Tsutsumi K., Shibata S., Inoue M., Mori K. [Experimental cerebral infarction in the dog. Ultrastructural study of microvessels in subacute cerebral infarction]. Neurol Med Chir (Tokyo) 1987 Feb;27(2):73–77. doi: 10.2176/nmc.27.73. [DOI] [PubMed] [Google Scholar]
- Tsutsumi K. [Experimental cerebral infarction in the dog. Scanning electron microscopy with vascular endocasts of microvessels in the ischemic brain]. Neurol Med Chir (Tokyo) 1986 Aug;26(8):595–600. doi: 10.2176/nmc.26.595. [DOI] [PubMed] [Google Scholar]
- del Zoppo G. J., Schmid-Schönbein G. W., Mori E., Copeland B. R., Chang C. M. Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke. 1991 Oct;22(10):1276–1283. doi: 10.1161/01.str.22.10.1276. [DOI] [PubMed] [Google Scholar]
- del Zoppo G. J., Yu J. Q., Copeland B. R., Thomas W. S., Schneiderman J., Morrissey J. H. Tissue factor localization in non-human primate cerebral tissue. Thromb Haemost. 1992 Dec 7;68(6):642–647. [PubMed] [Google Scholar]
- van Mourik J. A., Leeksma O. C., Reinders J. H., de Groot P. G., Zandbergen-Spaargaren J. Vascular endothelial cells synthesize a plasma membrane protein indistinguishable from the platelet membrane glycoprotein IIa. J Biol Chem. 1985 Sep 15;260(20):11300–11306. [PubMed] [Google Scholar]