Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1988 Sep;132(3):563–573.

Proliferative changes in the pulmonary arterial wall during short-term hyperoxic injury to the lung.

J T Coflesky 1, K B Adler 1, J Woodcock-Mitchell 1, J Mitchell 1, J N Evans 1
PMCID: PMC1880749  PMID: 3414783

Abstract

Injury to the lung during in vivo exposure to hyperoxia results in vascular restructuring and pulmonary hypertension. This study reports the pattern of cellular proliferation that occurs in proximal intrapulmonary arteries over time during vessel wall injury and adaptation to increased partial pressures of oxygen. Although the remodeling of the capillary bed has been emphasized particularly during oxygen injury to the lung, this report identifies significant proliferative changes within the vessel wall of proximal arterial segments isolated from rats exposed to 85% oxygen. An increased incorporation of 3H-thymidine by endothelial cells is the earliest and most dramatic vessel wall response. The labeling index of these cells is increased more than tenfold by the end of 7 days in hyperoxia. Proliferation of medial smooth muscle cells and adventitial fibroblasts is also significantly increased. The increased cell number within these compartments is noted especially for its contribution to the overall vessel wall hypertrophy observed in chronic hyperoxic pulmonary hypertension. This general proliferative response is accompanied by specific shifts in the relative percentages of different actin protein isoforms as identified by two-dimensional gel electrophoresis. Changes in the distribution of actin isoforms are discussed as potential markers of a phenotypic modulation among vascular smooth muscle cells that occurs during the progression of pulmonary vessel wall remodeling.

Full text

PDF
564

Images in this article

567Figure 4
on p.567
570Figure 9
on p.570

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barja F., Coughlin C., Belin D., Gabbiani G. Actin isoform synthesis and mRNA levels in quiescent and proliferating rat aortic smooth muscle cells in vivo and in vitro. Lab Invest. 1986 Aug;55(2):226–233. [PubMed] [Google Scholar]
  2. Bowden D. H., Adamson I. Y. Endothelial regeneration as a marker of the differential vascular responses in oxygen-induced pulmonary edema. Lab Invest. 1974 Mar;30(3):350–357. [PubMed] [Google Scholar]
  3. Chamley-Campbell J., Campbell G. R., Ross R. The smooth muscle cell in culture. Physiol Rev. 1979 Jan;59(1):1–61. doi: 10.1152/physrev.1979.59.1.1. [DOI] [PubMed] [Google Scholar]
  4. Clowes A. W., Clowes M. M. Kinetics of cellular proliferation after arterial injury. II. Inhibition of smooth muscle growth by heparin. Lab Invest. 1985 Jun;52(6):611–616. [PubMed] [Google Scholar]
  5. 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]
  6. Coflesky J. T., Jones R. C., Reid L. M., Evans J. N. Mechanical properties and structure of isolated pulmonary arteries remodeled by chronic hyperoxia. Am Rev Respir Dis. 1987 Aug;136(2):388–394. doi: 10.1164/ajrccm/136.2.388. [DOI] [PubMed] [Google Scholar]
  7. Crapo J. D., Freeman B. A., Barry B. E., Turrens J. F., Young S. L. Mechanisms of hyperoxic injury to the pulmonary microcirculation. Physiologist. 1983 Jun;26(3):170–176. [PubMed] [Google Scholar]
  8. Crapo J. D., Peters-Golden M., Marsh-Salin J., Shelburne J. S. Pathologic changes in the lungs of oxygen-adapted rats: a morphometric analysis. Lab Invest. 1978 Dec;39(6):640–653. [PubMed] [Google Scholar]
  9. Dilley R. J., McGeachie J. K., Prendergast F. J. A review of the proliferative behaviour, morphology and phenotypes of vascular smooth muscle. Atherosclerosis. 1987 Feb;63(2-3):99–107. doi: 10.1016/0021-9150(87)90109-2. [DOI] [PubMed] [Google Scholar]
  10. Jones R., Zapol W. M., Reid L. Pulmonary arterial wall injury and remodelling by hyperoxia. Chest. 1983 May;83(5 Suppl):40S–42S. doi: 10.1378/chest.83.5_supplement.40s. [DOI] [PubMed] [Google Scholar]
  11. Jones R., Zapol W. M., Reid L. Pulmonary artery remodeling and pulmonary hypertension after exposure to hyperoxia for 7 days. A morphometric and hemodynamic study. Am J Pathol. 1984 Nov;117(2):273–285. [PMC free article] [PubMed] [Google Scholar]
  12. Kocher O., Gabbiani G. Expression of actin mRNAs in rat aortic smooth muscle cells during development, experimental intimal thickening, and culture. Differentiation. 1986;32(3):245–251. doi: 10.1111/j.1432-0436.1986.tb00580.x. [DOI] [PubMed] [Google Scholar]
  13. Kocher O., Skalli O., Cerutti D., Gabbiani F., Gabbiani G. Cytoskeletal features of rat aortic cells during development. An electron microscopic, immunohistochemical, and biochemical study. Circ Res. 1985 Jun;56(6):829–838. doi: 10.1161/01.res.56.6.829. [DOI] [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Laemmli U. K., Favre M. Maturation of the head of bacteriophage T4. I. DNA packaging events. J Mol Biol. 1973 Nov 15;80(4):575–599. doi: 10.1016/0022-2836(73)90198-8. [DOI] [PubMed] [Google Scholar]
  16. Low R. B., Woodcock-Mitchell J., Evans J. N., Adler K. B. Actin content of normal and of bleomycin-fibrotic rat lung. Am Rev Respir Dis. 1984 Feb;129(2):311–316. [PubMed] [Google Scholar]
  17. Meyrick B., Reid L. Hypoxia and incorporation of 3H-thymidine by cells of the rat pulmonary arteries and alveolar wall. Am J Pathol. 1979 Jul;96(1):51–70. [PMC free article] [PubMed] [Google Scholar]
  18. Niedenzu C., Grasedyck K., Voelkel N. F., Bittmann S., Lindner J. Proliferation of lung cells in chronically hypoxic rats. An autoradiographic and radiochemical study. Int Arch Occup Environ Health. 1981;48(2):185–193. doi: 10.1007/BF00378440. [DOI] [PubMed] [Google Scholar]
  19. Nilsson J. Growth factors and the pathogenesis of atherosclerosis. Atherosclerosis. 1986 Dec;62(3):185–199. doi: 10.1016/0021-9150(86)90093-6. [DOI] [PubMed] [Google Scholar]
  20. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  21. Owens G. K., Rabinovitch P. S., Schwartz S. M. Smooth muscle cell hypertrophy versus hyperplasia in hypertension. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7759–7763. doi: 10.1073/pnas.78.12.7759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pinkerton K. E., Barry B. E., O'Neil J. J., Raub J. A., Pratt P. C., Crapo J. D. Morphologic changes in the lung during the lifespan of Fischer 344 rats. Am J Anat. 1982 Jun;164(2):155–174. doi: 10.1002/aja.1001640206. [DOI] [PubMed] [Google Scholar]
  23. Reidy M. A. A reassessment of endothelial injury and arterial lesion formation. Lab Invest. 1985 Nov;53(5):513–520. [PubMed] [Google Scholar]
  24. Reidy M. A., Chao S. S., Kirkman T. R., Clowes A. W. Endothelial regeneration. VI. Chronic nondenuding injury in baboon vascular grafts. Am J Pathol. 1986 Jun;123(3):432–439. [PMC free article] [PubMed] [Google Scholar]
  25. Ross R., Raines E. W., Bowen-Pope D. F. The biology of platelet-derived growth factor. Cell. 1986 Jul 18;46(2):155–169. doi: 10.1016/0092-8674(86)90733-6. [DOI] [PubMed] [Google Scholar]
  26. Ross R. The pathogenesis of atherosclerosis--an update. N Engl J Med. 1986 Feb 20;314(8):488–500. doi: 10.1056/NEJM198602203140806. [DOI] [PubMed] [Google Scholar]
  27. Schwartz S. M., Campbell G. R., Campbell J. H. Replication of smooth muscle cells in vascular disease. Circ Res. 1986 Apr;58(4):427–444. doi: 10.1161/01.res.58.4.427. [DOI] [PubMed] [Google Scholar]
  28. Schwartz S. M. Hypertension as a vascular response to injury. Hypertension. 1984 Nov-Dec;6(6 Pt 2):III33–III37. doi: 10.1161/01.hyp.6.6_pt_2.iii33. [DOI] [PubMed] [Google Scholar]
  29. Skalli O., Bloom W. S., Ropraz P., Azzarone B., Gabbiani G. Cytoskeletal remodeling of rat aortic smooth muscle cells in vitro: relationships to culture conditions and analogies to in vivo situations. J Submicrosc Cytol. 1986 Jul;18(3):481–493. [PubMed] [Google Scholar]
  30. Thyberg J., Nilsson J., Palmberg L., Sjölund M. Adult human arterial smooth muscle cells in primary culture. Modulation from contractile to synthetic phenotype. Cell Tissue Res. 1985;239(1):69–74. doi: 10.1007/BF00214904. [DOI] [PubMed] [Google Scholar]
  31. Warshaw D. M., Szarek J. L., Hubbard M. S., Evans J. N. Pharmacology and force development of single freshly isolated bovine carotid artery smooth muscle cells. Circ Res. 1986 Mar;58(3):399–406. doi: 10.1161/01.res.58.3.399. [DOI] [PubMed] [Google Scholar]
  32. Wray W., Boulikas T., Wray V. P., Hancock R. Silver staining of proteins in polyacrylamide gels. Anal Biochem. 1981 Nov 15;118(1):197–203. doi: 10.1016/0003-2697(81)90179-2. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES