Abstract
An immunocytochemical and cytochemical study has been made on the ultrastructural localisation of type III (endothelial) nitric oxide synthase, endothelin-1 and the binding sites of lectin from Bandeirea simplicifolia to the endothelium surface-associated glycoproteins in the rat left common carotid artery at 1 and 28 d after Fogarty embolectomy balloon catheter-induced injury. Controls were carotid arteries from sham operated rats. In the controls, the immunoreactivity to nitric oxide synthase-III and endothelin-1 was localised in different proportions in vascular endothelial cells (36·9%±4·3 and 7·6%±2·7, respectively); immunoreactivity was confined to the cytoplasm and the membranes of intracellular organelles and structures. In contrast, staining with lectin was localised on the luminal surface of all endothelial cells. 1 d after injury, platelets were adherent to the endothelium-denuded intima. Some of the platelets displayed immunoreactivity to nitric oxide synthase-III and endothelin-1 and were stained with lectin. 28 d after injury, a neointimal thickening of substantial size was present. Subpopulations of the regrown endothelial cells covering the luminal surface of the neointima showed positive immunoreactivity to nitric oxide synthase-III and endothelin-1 but there was a significant decrease in the proportion of nitric oxide synthase-III-containing endothelial cells (17·2%±1·9; P < 0·001) and a significant increase in the proportion of endothelin-1-containing endothelial cells (36·9%±4·7; P < 0·001) compared with the controls. Staining with lectin was associated with the cell membrane of all endothelial cells and in addition with cells located ‘deeper’ in the neointima which showed lectin-positive plasmalemma, Golgi complex and multivesicular bodies/lysosomes. In conclusion, regenerated endothelial cells of the neointima showed reduced population (2–fold) of nitric oxide synthase-III- and increased population (5–fold) endothelin-1-positive cells. The subendothelial location of some lectin-stained cells after balloon catheter injury indicates the heterogeneity of the neointima and suggests that some of these cells are involved in early angiogenesis. 24 h and 28 d after injury some platelets showed positive immunoreactivity for nitric oxide synthase-III and endothelin-1.
Keywords: Vasculature, endothelium, vasoactive agents, glycoproteins, angioplasty
Full Text
The Full Text of this article is available as a PDF (1.3 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barger A. C., Beeuwkes R., 3rd, Lainey L. L., Silverman K. J. Hypothesis: vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. N Engl J Med. 1984 Jan 19;310(3):175–177. doi: 10.1056/NEJM198401193100307. [DOI] [PubMed] [Google Scholar]
- Bodin P., Milner P., Winter R., Burnstock G. Chronic hypoxia changes the ratio of endothelin to ATP release from rat aortic endothelial cells exposed to high flow. Proc Biol Sci. 1992 Feb 22;247(1319):131–135. doi: 10.1098/rspb.1992.0019. [DOI] [PubMed] [Google Scholar]
- Booth R. F., Martin J. F., Honey A. C., Hassall D. G., Beesley J. E., Moncada S. Rapid development of atherosclerotic lesions in the rabbit carotid artery induced by perivascular manipulation. Atherosclerosis. 1989 Apr;76(2-3):257–268. doi: 10.1016/0021-9150(89)90109-3. [DOI] [PubMed] [Google Scholar]
- Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
- Clowes A. W., Reidy M. A., Clowes M. M. Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. Lab Invest. 1983 Sep;49(3):327–333. [PubMed] [Google Scholar]
- Coffin J. D., Harrison J., Schwartz S., Heimark R. Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo. Dev Biol. 1991 Nov;148(1):51–62. doi: 10.1016/0012-1606(91)90316-u. [DOI] [PubMed] [Google Scholar]
- Davies P. F. Vascular cell interactions with special reference to the pathogenesis of atherosclerosis. Lab Invest. 1986 Jul;55(1):5–24. [PubMed] [Google Scholar]
- Dinarello C. A. An update on human interleukin-1: from molecular biology to clinical relevance. J Clin Immunol. 1985 Sep;5(5):287–297. doi: 10.1007/BF00918247. [DOI] [PubMed] [Google Scholar]
- Fingerle J., Johnson R., Clowes A. W., Majesky M. W., Reidy M. A. Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8412–8416. doi: 10.1073/pnas.86.21.8412. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
- Förstermann U., Schmidt H. H., Pollock J. S., Sheng H., Mitchell J. A., Warner T. D., Nakane M., Murad F. Isoforms of nitric oxide synthase. Characterization and purification from different cell types. Biochem Pharmacol. 1991 Oct 24;42(10):1849–1857. doi: 10.1016/0006-2952(91)90581-o. [DOI] [PubMed] [Google Scholar]
- Gorelova E., Loesch A., Bodin P., Chadwick L., Hamlyn P. J., Burnstock G. Localisation of immunoreactive factor VIII, nitric oxide synthase, substance P, endothelin-1 and 5-hydroxytryptamine in human postmortem middle cerebral artery. J Anat. 1996 Feb;188(Pt 1):97–107. [PMC free article] [PubMed] [Google Scholar]
- Hirata Y., Takagi Y., Fukuda Y., Marumo F. Endothelin is a potent mitogen for rat vascular smooth muscle cells. Atherosclerosis. 1989 Aug;78(2-3):225–228. doi: 10.1016/0021-9150(89)90227-x. [DOI] [PubMed] [Google Scholar]
- Holthöfer H., Virtanen I., Kariniemi A. L., Hormia M., Linder E., Miettinen A. Ulex europaeus I lectin as a marker for vascular endothelium in human tissues. Lab Invest. 1982 Jul;47(1):60–66. [PubMed] [Google Scholar]
- Hormia M., Lehto V. P., Virtanen I. Identification of UEA I-binding surface glycoproteins of cultured human endothelial cells. Cell Biol Int Rep. 1983 Jun;7(6):467–475. doi: 10.1016/0309-1651(83)90136-4. [DOI] [PubMed] [Google Scholar]
- Jackson C. J., Garbett P. K., Nissen B., Schrieber L. Binding of human endothelium to Ulex europaeus I-coated Dynabeads: application to the isolation of microvascular endothelium. J Cell Sci. 1990 Jun;96(Pt 2):257–262. doi: 10.1242/jcs.96.2.257. [DOI] [PubMed] [Google Scholar]
- Joly G. A., Schini V. B., Vanhoutte P. M. Balloon injury and interleukin-1 beta induce nitric oxide synthase activity in rat carotid arteries. Circ Res. 1992 Aug;71(2):331–338. doi: 10.1161/01.res.71.2.331. [DOI] [PubMed] [Google Scholar]
- Klimaschewski L., Kummer W., Mayer B., Couraud J. Y., Preissler U., Philippin B., Heym C. Nitric oxide synthase in cardiac nerve fibers and neurons of rat and guinea pig heart. Circ Res. 1992 Dec;71(6):1533–1537. doi: 10.1161/01.res.71.6.1533. [DOI] [PubMed] [Google Scholar]
- Laitinen L. Griffonia simplicifolia lectins bind specifically to endothelial cells and some epithelial cells in mouse tissues. Histochem J. 1987 Apr;19(4):225–234. doi: 10.1007/BF01680633. [DOI] [PubMed] [Google Scholar]
- Lindner V., Lappi D. A., Baird A., Majack R. A., Reidy M. A. Role of basic fibroblast growth factor in vascular lesion formation. Circ Res. 1991 Jan;68(1):106–113. doi: 10.1161/01.res.68.1.106. [DOI] [PubMed] [Google Scholar]
- Lindner V., Majack R. A., Reidy M. A. Basic fibroblast growth factor stimulates endothelial regrowth and proliferation in denuded arteries. J Clin Invest. 1990 Jun;85(6):2004–2008. doi: 10.1172/JCI114665. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Loesch A., Bodin P., Burnstock G. Colocalization of endothelin, vasopressin and serotonin in cultured endothelial cells of rabbit aorta. Peptides. 1991 Sep-Oct;12(5):1095–1103. doi: 10.1016/0196-9781(91)90065-w. [DOI] [PubMed] [Google Scholar]
- Loesch A., Burnstock G. Ultrastructural localisation of serotonin and substance P in vascular endothelial cells of rat femoral and mesenteric arteries. Anat Embryol (Berl) 1988;178(2):137–142. doi: 10.1007/BF02463647. [DOI] [PubMed] [Google Scholar]
- Loesch A., Burnstock G. Ultrastructural localization of nitric oxide synthase and endothelin in coronary and pulmonary arteries of newborn rats. Cell Tissue Res. 1995 Mar;279(3):475–483. doi: 10.1007/BF00318161. [DOI] [PubMed] [Google Scholar]
- Loesch A., Burnstock G. Ultrastructural localization of nitric oxide synthase and endothelin in rat pulmonary artery and vein during postnatal development and ageing. Cell Tissue Res. 1996 Mar;283(3):355–365. doi: 10.1007/s004410050546. [DOI] [PubMed] [Google Scholar]
- Loesch A., Domer F. R., Alexander B., Burnstock G. Electron-immunocytochemistry of peptides in endothelial cells of rabbit cerebral vessels following perfusion with a perfluorocarbon emulsion. Brain Res. 1993 May 21;611(2):333–337. doi: 10.1016/0006-8993(93)90522-o. [DOI] [PubMed] [Google Scholar]
- Lüscher T. F. Platelet-vessel wall interaction: role of nitric oxide, prostaglandins and endothelins. Baillieres Clin Haematol. 1993 Sep;6(3):609–627. doi: 10.1016/s0950-3536(05)80191-x. [DOI] [PubMed] [Google Scholar]
- McBride W., Lange R. A., Hillis L. D. Restenosis after successful coronary angioplasty. Pathophysiology and prevention. N Engl J Med. 1988 Jun 30;318(26):1734–1737. doi: 10.1056/NEJM198806303182606. [DOI] [PubMed] [Google Scholar]
- Milner P., Bodin P., Loesch A., Burnstock G. Rapid release of endothelin and ATP from isolated aortic endothelial cells exposed to increased flow. Biochem Biophys Res Commun. 1990 Jul 31;170(2):649–656. doi: 10.1016/0006-291x(90)92141-l. [DOI] [PubMed] [Google Scholar]
- Miyauchi T., Tomobe Y., Shiba R., Ishikawa T., Yanagisawa M., Kimura S., Sugishita Y., Ito I., Goto K., Masaki T. Involvement of endothelin in the regulation of human vascular tonus. Potent vasoconstrictor effect and existence in endothelial cells. Circulation. 1990 Jun;81(6):1874–1880. doi: 10.1161/01.cir.81.6.1874. [DOI] [PubMed] [Google Scholar]
- Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
- Nabel E. G., Yang Z. Y., Plautz G., Forough R., Zhan X., Haudenschild C. C., Maciag T., Nabel G. J. Recombinant fibroblast growth factor-1 promotes intimal hyperplasia and angiogenesis in arteries in vivo. Nature. 1993 Apr 29;362(6423):844–846. doi: 10.1038/362844a0. [DOI] [PubMed] [Google Scholar]
- Nathan C. F. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. doi: 10.1172/JCI112815. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nozaki K., Moskowitz M. A., Maynard K. I., Koketsu N., Dawson T. M., Bredt D. S., Snyder S. H. Possible origins and distribution of immunoreactive nitric oxide synthase-containing nerve fibers in cerebral arteries. J Cereb Blood Flow Metab. 1993 Jan;13(1):70–79. doi: 10.1038/jcbfm.1993.9. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
- Pollock J. S., Nakane M., Buttery L. D., Martinez A., Springall D., Polak J. M., Förstermann U., Murad F. Characterization and localization of endothelial nitric oxide synthase using specific monoclonal antibodies. Am J Physiol. 1993 Nov;265(5 Pt 1):C1379–C1387. doi: 10.1152/ajpcell.1993.265.5.C1379. [DOI] [PubMed] [Google Scholar]
- Radomski M. W., Moncada S. Regulation of vascular homeostasis by nitric oxide. Thromb Haemost. 1993 Jul 1;70(1):36–41. [PubMed] [Google Scholar]
- Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993 Apr 29;362(6423):801–809. doi: 10.1038/362801a0. [DOI] [PubMed] [Google Scholar]
- Sase K., Michel T. Expression of constitutive endothelial nitric oxide synthase in human blood platelets. Life Sci. 1995;57(22):2049–2055. doi: 10.1016/0024-3205(95)02191-k. [DOI] [PubMed] [Google Scholar]
- Sexton A. J., Loesch A., Turmaine M., Miah S., Burnstock G. Electron-microscopic immunolabelling of vasoactive substances in human umbilical endothelial cells and their actions in early and late pregnancy. Cell Tissue Res. 1996 Apr;284(1):167–175. doi: 10.1007/s004410050577. [DOI] [PubMed] [Google Scholar]
- Sexton A. J., Loesch A., Turmaine M., Miah S., Burnstock G. Nitric oxide and human umbilical vessels: pharmacological and immunohistochemical studies. Placenta. 1995 Apr;16(3):277–288. doi: 10.1016/0143-4004(95)90114-0. [DOI] [PubMed] [Google Scholar]
- Shimokawa H., Flavahan N. A., Vanhoutte P. M. Natural course of the impairment of endothelium-dependent relaxations after balloon endothelium removal in porcine coronary arteries. Possible dysfunction of a pertussis toxin-sensitive G protein. Circ Res. 1989 Sep;65(3):740–753. doi: 10.1161/01.res.65.3.740. [DOI] [PubMed] [Google Scholar]
- Springall D. R., Riveros-Moreno V., Buttery L., Suburo A., Bishop A. E., Merrett M., Moncada S., Polak J. M. Immunological detection of nitric oxide synthase(s) in human tissues using heterologous antibodies suggesting different isoforms. Histochemistry. 1992 Nov;98(4):259–266. doi: 10.1007/BF00271040. [DOI] [PubMed] [Google Scholar]
- Tomlinson A., Van Vlijmen H., Loesch A., Burnstock G. An immunohistochemical study of endothelial cell heterogeneity in the rat: observations in "en face" Häutchen preparations. Cell Tissue Res. 1991 Jan;263(1):173–181. doi: 10.1007/BF00318413. [DOI] [PubMed] [Google Scholar]
- Vanhoutte P. M. Hypercholesterolaemia, atherosclerosis and release of endothelium-derived relaxing factor by aggregating platelets. Eur Heart J. 1991 Nov;12 (Suppl E):25–32. doi: 10.1093/eurheartj/12.suppl_e.25. [DOI] [PubMed] [Google Scholar]
- Wheeler C. H., Collins A., Dunn M. J., Crisp S. J., Yacoub M. H., Rose M. L. Characterization of endothelial antigens associated with transplant-associated coronary artery disease. J Heart Lung Transplant. 1995 Nov-Dec;14(6 Pt 2):S188–S197. [PubMed] [Google Scholar]
- Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]