Virchows Archiv A

, Volume 408, Issue 6, pp 559–574 | Cite as

Time course of arterial repair following endothelial denudation in the rat carotid artery

A morphometric study in Wistar and Sprague-Dawley rats
  • Elizabeth van Pelt-Verkuil
  • Jan Knoester
  • Wilfrid van Pelt
  • Marijke Brink
  • Dick Jense
  • Jef J. Emeis


Repair processes in the intima and media of the rat carotid artery were studied morphometrically for time intervals of up to 28 days after injury induced by air-drying. Air-drying injury included endothelial denudation as well as medial necrosis.

Repair was most rapid between days 9 and 11 after injury as regards the increase in myointimal lesion size, the extent of repopulation of the media and re-endothelialization. After day 11, myointimal lesion size continued to increase until day 28. Medial repair, however, almost completely ceased at day 11, 25% of the inner media and 5% of the outer media remaining necrotic. At day 21, the vessels were almost completely re-endothelialized; however, even at day 28, about 10% of the middle of the vessel was still permeable to Evans Blue.

The response of Sprague Dawley rats to injury differed from that of Wistar rats. Compared with Wistar rats, Sprague Dawley rats showed larger myointimal lesions, less medial necrosis and slower endothelial repair. It is suggested that the extent of medial necrosis and the speed of endothelial regeneration affect the arteriosclerotic response in rats

Key words

Endothelial denudation Medial necrosis Arteriosclerosis Rat Carotid artery 


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  1. Björkerud S, Bondjers G (1971) Arterial repair and atherosclerosis after mechanical injury. Part 2. Tissue response after induction of a total local necrosis (deep longitudinal injury). Atherosclerosis 14:259–276Google Scholar
  2. Björkerud S, Bondjers G (1973) Arterial repair and atherosclerosis after mechanical injury. Part 5. Tissue response after induction of a large superficial transversal injury. Atherosclerosis 18:235–255Google Scholar
  3. Bondjers G, Björnheden T (1970) Experimental atherosclerosis induced by mechanical trauma in rats. Atherosclerosis 12:301–306Google Scholar
  4. Bruhn HD (1981) Growth regulation of vessel wall cells and of tumor cells by thrombin, Factor XIII and fibronectin.Thromb Haemost 46:762Google Scholar
  5. Burns ER, Spaet TH, Stemerman MB (1978) Response of the arterial wall to endothelial removal: an autoradiographic study. Proc Soc Exp Biol Med 159:473–477Google Scholar
  6. Clowes AW, Clowes MM (1980) The influence of hypertension on injury-induced myointimal thickening. Surgery 88:254–259Google Scholar
  7. Clowes AW, Ryan GB, Breslow JL, Karnovsky MJ (1976) Absence of enhanced intimal thickening in the response of the carotid arterial wall to endothelial injury in hypercholesterolemic rats. Lab Invest 35:6–16Google Scholar
  8. Clowes AW, Callazzo RE, Karnovsky MJ (1978) A morphologic and permeability study of luminal smooth muscle cells after arterial injury in the rat. Lab Invest 39:141–150Google Scholar
  9. Falcone DJ, Hajjar DP, Minick CR (1980) Enhancement of cholesterol and cholesterylester accumulation in re-endothelialized aorta. Am J Pathol 99:81–104Google Scholar
  10. Fishman JA, Ryan GB, Karnovsky MJ (1975) Endothelial regeneration in the rat carotid artery and the significance of endothelial denudation in the pathogenesis of myointimal thickening. Lab Invest 32:339–351Google Scholar
  11. Goldberg ID, Stemerman MD, Ransil BJ, Fuhra RL (1980) In vivo aortic muscle cell growth kinetics. Differences between thoracic and abdominal segments after intimal injury in the rabbit. Circ Res 47:182–189Google Scholar
  12. Grotendorst GR, Chang T, Seppā HEJ, Kleinman HK, Martin GR (1982) Platelet derived growth factor is a chemoattractant for vascular smooth muscle cells. J Cell Physiol 113:261–266Google Scholar
  13. Guyton JR, Rosenberg RD, Clowes AW, Karnovsky MJ (1980) Inhibition of rat arterial smooth muscle cell proliferation by heparin. In vivo studies with anticoagulant and non-anticoagulant heparin. Circ Res 46:625–634Google Scholar
  14. Hassler O (1970) The origin of the cells constituting arterial intima thickening. An experimental autoradiographic study with the use of H3-thymidine. Lab Invest 22:286–293Google Scholar
  15. Haudenschild CC, Schwartz SM (1979) Endothelial regeneration. II Restitution of endothelial continuity. Lab Invest 41:407–418Google Scholar
  16. Haudenschild CC, Van Sickle W, Chobanian AV (1981) Response of the aorta of the obese Zucker rat to injury. Arteriosclerosis 1:186–191Google Scholar
  17. Hirsch EZ, Robertson AL (1977) Selective acute arterial endothelial injury and repair. I Methodology and surface characteristics. Atherosclerosis 28:271–287Google Scholar
  18. Ishida T, Tanaka K (1982) Effects of fibrin and fibrinogen degradation products on the growth of rabbit aortic smooth muscle cells in culture. Atherosclerosis 44:161–174Google Scholar
  19. Karnovsky MJ (1981) Endothelial-vascular smooth muscle cell interactions. Am J Pathol 105:200–206Google Scholar
  20. Koletski S, Snajdar RM (1981) Atherosclerosis following balloon catheter injury to the carotid artery and the aorta of hypertensive rats with normolipidemia or hyperlipidemia. Am J Pathol 103:105–115Google Scholar
  21. Lecker D, Kumar A (1980) Effects of 6-(p-(4-phenyl acetylpiperazin-L-yl)-phenyl)-4.5-dinitro-3(2H7-pyridazinone (CCI 17810) and aspirin on experimental arterial thrombosis in rats. Thromb Haemost 44:9–11Google Scholar
  22. Van Pelt-Verkuil E, Van Pelt W, Jense D (1983) Morphometry of air-drying induced arteriosclerosis in rat carotid artery: the effect of the air-flow rate. Arteriosclerosis 3:441–451Google Scholar
  23. Poole JCF, Cromwell SB, Benditt EP (1971) Behavior of smooth muscle cells and formation of extracellular structures in the reaction of arterial walls to injury. Am J Pathol 62:391–413Google Scholar
  24. Reidy MA, Standaert D, Schwartz SM (1982) Inhibition of endothelial cell regrowth. Cessation of aortic endothelial cell replication after balloon catheter denudation. Arteriosclerosis 2:216–220Google Scholar
  25. Ross R (1981) Atherosclerosis: a problem of the biology of arterial wall cells and their interactions with blood components. Arteriosclerosis 1:293–311Google Scholar
  26. Ross R, Glomset J (1973) Atherosclerosis and the arterial smooth muscle cell. Science 180:1332–1339Google Scholar
  27. Ross R, Glomset J (1976) The pathogenesis of atherosclerosis. N Engl J Med 295:369–377; 420–425Google Scholar
  28. Schwartz SM, Stemerman MB, Benditt EP (1975) The aortic intima. II Repair of the arotic lining after mechanical denudation. Am J Pathol 81:15–42Google Scholar
  29. Spaet TH, Stemerman MB, Veith FJ, Lejnieks I (1975) Intimal injury of neointima. Circ Res 36:58–70Google Scholar
  30. Subbiah MTR (1976) White Carneau pigeon: an ideal model for the study of progression and regression of atherosclerosis. Biochem Exp Biol 12:229–234Google Scholar
  31. Thorgeirsson G, Robertson AL (1978) The vascular endothelium - Pathobiologic significance. Am J Pathol 93:802–848Google Scholar
  32. Thorgeirsson G, Robertson AL, Cowan DH (1979) Migration of human vascular endothelial and smooth muscle cells. Lab Invest 41:51–62Google Scholar
  33. Tiell ML, Stemerman MB, Spaet TH (1978) The influence of the pituitary on arterial intimal proliferation in the rat. Circ Res 42:644–649Google Scholar
  34. Tiell ML, Sussman II, Moss R, Drouet LC, Spaet TH (1982) Production of experimental arteriosclerosis in Fawn-Hooded rats with platelet storage pool deficincy. Artery 10:329–340Google Scholar
  35. Wagner WD, Clarkson TB, Feldner MA, Prichard RW (1973) The development of pigeon strains with selected atherosclerosis characteristics. Exp Mol Pathol 19:304–319Google Scholar
  36. Yamori Y, Igawa T, Kanbe T, Kihara M, Nara Y, Horie R (1981) Mechanisms of structural vascular changes in genetic hypertension: analyses on cultured vascular smooth muscle cells from spontaneous hypertensive rats. Clin Sci 61:121S-123SGoogle Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Elizabeth van Pelt-Verkuil
    • 1
  • Jan Knoester
    • 1
  • Wilfrid van Pelt
    • 1
  • Marijke Brink
    • 1
  • Dick Jense
    • 1
  • Jef J. Emeis
    • 1
  1. 1.TNO Gaubius Institute for Cardiovascular ResearchLeidenThe Netherlands

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