Abstract
Intimal thickening induced after endothelial denudation of rat aorta is though to be due to migration and proliferation of smooth muscle cells (SMC). When the reendothelialization is achieved, intimal thickening shows an important decrease in cellularity. Using in situ end labeling of fragmented DNA and electron microscopy, we show that this remodeling is accompanied by apoptosis of SMC. The number of apoptotic SMC becomes important 15 days after endothelial injury and reaches a maximum at 20 days; at 45 days the intimal thickening is reendothelialized and no more apoptotic SMC are detected. Apoptotic SMC show nuclear and cytoplasmic condensation as well as cytoplasmic vacuolization. Our results indicate that apoptosis is an important mechanism in the regulation of intimal thickening evolution.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baumgartner H. R., Studer A. Folgen des Gefässkatheterismus am normo- und hypercholesterinaemischen Kaninchen. Pathol Microbiol (Basel) 1966;29(4):393–405. [PubMed] [Google Scholar]
- Bennett M. R., Anglin S., McEwan J. R., Jagoe R., Newby A. C., Evan G. I. Inhibition of vascular smooth muscle cell proliferation in vitro and in vivo by c-myc antisense oligodeoxynucleotides. J Clin Invest. 1994 Feb;93(2):820–828. doi: 10.1172/JCI117036. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bennett M. R., Evan G. I., Newby A. C. Deregulated expression of the c-myc oncogene abolishes inhibition of proliferation of rat vascular smooth muscle cells by serum reduction, interferon-gamma, heparin, and cyclic nucleotide analogues and induces apoptosis. Circ Res. 1994 Mar;74(3):525–536. doi: 10.1161/01.res.74.3.525. [DOI] [PubMed] [Google Scholar]
- Benzonana G., Skalli O., Gabbiani G. Correlation between the distribution of smooth muscle or non muscle myosins and alpha-smooth muscle actin in normal and pathological soft tissues. Cell Motil Cytoskeleton. 1988;11(4):260–274. doi: 10.1002/cm.970110405. [DOI] [PubMed] [Google Scholar]
- Biro S., Fu Y. M., Yu Z. X., Epstein S. E. Inhibitory effects of antisense oligodeoxynucleotides targeting c-myc mRNA on smooth muscle cell proliferation and migration. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):654–658. doi: 10.1073/pnas.90.2.654. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Björkerud S., Björkerud B., Joelsson M. Structural organization of reconstituted human arterial smooth muscle tissue. Arterioscler Thromb. 1994 Apr;14(4):644–651. doi: 10.1161/01.atv.14.4.644. [DOI] [PubMed] [Google Scholar]
- Bobik A., Campbell J. H. Vascular derived growth factors: cell biology, pathophysiology, and pharmacology. Pharmacol Rev. 1993 Mar;45(1):1–42. [PubMed] [Google Scholar]
- Bochaton-Piallat M. L., Gabbiani F., Ropraz P., Gabbiani G. Age influences the replicative activity and the differentiation features of cultured rat aortic smooth muscle cell populations and clones. Arterioscler Thromb. 1993 Oct;13(10):1449–1455. doi: 10.1161/01.atv.13.10.1449. [DOI] [PubMed] [Google Scholar]
- Bursch W., Oberhammer F., Schulte-Hermann R. Cell death by apoptosis and its protective role against disease. Trends Pharmacol Sci. 1992 Jun;13(6):245–251. doi: 10.1016/0165-6147(92)90077-j. [DOI] [PubMed] [Google Scholar]
- Campbell G. R., Campbell J. H. The phenotypes of smooth muscle expressed in human atheroma. Ann N Y Acad Sci. 1990;598:143–158. doi: 10.1111/j.1749-6632.1990.tb42286.x. [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]
- Kane A. B. Redefining cell death. Am J Pathol. 1995 Jan;146(1):1–2. [PMC free article] [PubMed] [Google Scholar]
- Kerr J. F., Winterford C. M., Harmon B. V. Apoptosis. Its significance in cancer and cancer therapy. Cancer. 1994 Apr 15;73(8):2013–2026. doi: 10.1002/1097-0142(19940415)73:8<2013::aid-cncr2820730802>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
- Kocher O., Skalli O., Bloom W. S., Gabbiani G. Cytoskeleton of rat aortic smooth muscle cells. Normal conditions and experimental intimal thickening. Lab Invest. 1984 Jun;50(6):645–652. [PubMed] [Google Scholar]
- Kockx M. M., Cambier B. A., Bortier H. E., De Meyer G. R., Declercq S. C., van Cauwelaert P. A., Bultinck J. Foam cell replication and smooth muscle cell apoptosis in human saphenous vein grafts. Histopathology. 1994 Oct;25(4):365–371. doi: 10.1111/j.1365-2559.1994.tb01355.x. [DOI] [PubMed] [Google Scholar]
- Lemire J. M., Covin C. W., White S., Giachelli C. M., Schwartz S. M. Characterization of cloned aortic smooth muscle cells from young rats. Am J Pathol. 1994 May;144(5):1068–1081. [PMC free article] [PubMed] [Google Scholar]
- Orlandi A., Ehrlich H. P., Ropraz P., Spagnoli L. G., Gabbiani G. Rat aortic smooth muscle cells isolated from different layers and at different times after endothelial denudation show distinct biological features in vitro. Arterioscler Thromb. 1994 Jun;14(6):982–989. doi: 10.1161/01.atv.14.6.982. [DOI] [PubMed] [Google Scholar]
- Osborn M., Caselitz J., Püschel K., Weber K. Intermediate filament expression in human vascular smooth muscle and in arteriosclerotic plaques. Virchows Arch A Pathol Anat Histopathol. 1987;411(5):449–458. doi: 10.1007/BF00735226. [DOI] [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]
- Schmitt-Gräff A., Chakroun G., Gabbiani G. Modulation of perisinusoidal cell cytoskeletal features during experimental hepatic fibrosis. Virchows Arch A Pathol Anat Histopathol. 1993;422(2):99–107. doi: 10.1007/BF01607161. [DOI] [PubMed] [Google Scholar]
- Schwartz S. M., Heimark R. L., Majesky M. W. Developmental mechanisms underlying pathology of arteries. Physiol Rev. 1990 Oct;70(4):1177–1209. doi: 10.1152/physrev.1990.70.4.1177. [DOI] [PubMed] [Google Scholar]
- Shi Y., Hutchinson H. G., Hall D. J., Zalewski A. Downregulation of c-myc expression by antisense oligonucleotides inhibits proliferation of human smooth muscle cells. Circulation. 1993 Sep;88(3):1190–1195. doi: 10.1161/01.cir.88.3.1190. [DOI] [PubMed] [Google Scholar]
- Skalli O., Ropraz P., Trzeciak A., Benzonana G., Gillessen D., Gabbiani G. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol. 1986 Dec;103(6 Pt 2):2787–2796. doi: 10.1083/jcb.103.6.2787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wight T. N. Cell biology of arterial proteoglycans. Arteriosclerosis. 1989 Jan-Feb;9(1):1–20. doi: 10.1161/01.atv.9.1.1. [DOI] [PubMed] [Google Scholar]
- Wijsman J. H., Jonker R. R., Keijzer R., van de Velde C. J., Cornelisse C. J., van Dierendonck J. H. A new method to detect apoptosis in paraffin sections: in situ end-labeling of fragmented DNA. J Histochem Cytochem. 1993 Jan;41(1):7–12. doi: 10.1177/41.1.7678025. [DOI] [PubMed] [Google Scholar]
- van Neck J. W., Bloemers H. P. Molecular aspects of pathological processes in the artery wall. Mol Biol Rep. 1992 Nov;17(1):1–15. doi: 10.1007/BF01006394. [DOI] [PubMed] [Google Scholar]