Summary
Cell size distribution and growth rates were studied in vitro in human plaque cells from advanced primary stenosing and fresh restenosing lesions of peripheral and coronary arteries. Cells were isolated either by the explant technique or by enzymatic disaggregation and were identified as smooth muscle cells by their typical growth pattern and their positive reaction with antibodies against smooth muscle α-actin. Endothelial cells were found in plaque specimens from coronary arteries but were only present in primary cultures. Smooth muscle cells from primary stenosing tissue (ps-SMC) exhibited a significantly lower growth rate in culture (0.15±0.04 population doublings per day; \(\bar x \pm SD\)) compared with cells from restenosing lesions (re-SMC; 0.60±0.13 population doublings per day; \(\bar x \pm SD\)). ps-SMC usually became senescent in their second passage, i.e., after 5–7 cumultive population doublings. re-SMC retained their high proliferative activity even after five passages (15 cumulative population doublings). Cell populations of both origins consisted of two distinct subpopulations which could be discriminated by cell size measurements: relatively small, predominant cells (cell diameter: 18.0±4 μm; \(\bar x \pm SD\)) and large fibroblast-like cells (cell diameter: 26.0±3 μm; \(\bar x \pm SD\)). The proportion of large cells was higher in cell populations derived from primary stenosing tissue. These results suggest that stenosing plaque tissue from human peripheral and coronary arteries consists of two smooth muscle cell subpopulations. The low proliferative activity of total smooth muscle cell populations of advanced primary stenosing lesions contrasts with the high mitotic activity of smooth muscle cells obtained from secondary stenosing intimal proliferates.
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References
Bauriedel G, Dartsch PC, Voisard R, Roth D, Simpson JB, Höfling B, Betz E (1989) Selective percutaneous “biopsy” of atheromatous plaque tissue for cell culture. Basic Res Cardiol 84:326–331
Benditt EP, Benditt JM (1973) Evidence for a monoclonal origin of human atherosclerotic plaques. Proc Natl Acad Sci USA 70:1753–1756
Björkerud S (1985) Cultivated human arterial smooth muscle displays heterogenous pattern of growth and phenotypic variation. Lab Invest 53:303–310
Björkerud S, Ekroth R (1980) The growth of human atherosclerotic and non-atherosclerotic aortic intima and media in vitro. Artery 8:329–335
Campbell GR, Cambell JH (1981) The cellular pathology of atherosclerosis. Pathology 13:423–440
Campbell GR, Campbell JH (1985) Smooth muscle phenotypic changes in arterial wall homeostasis: implications for the pathogenesis of atherosclerosis. Exp Mol Pathol 42: 139–162
Dartsch PC (1987) Das Zellskelett von kultivierten Gefäßwandzellen. Mikrokosmos 76: 33–39
Dartsch PC, Roth D, Betz E (1988) Gefäßwandzellen des Menschen in Kultur. VASA [Suppl] 23:18–22
Dartsch PC, Bauriedel G, Höfling B, Betz E (1989) Cell culture of human atheromatous plaque material. In: Höfling B, v Pölnitz A (eds) Interventional cardiology and angiology. Steinkopff, Darmstadt, pp 115–125
Dartsch PC, Bauriedel G, Schinko I, Weiss HD, Höfling B, Betz E (1989) Cell constitution and characteristics of human atherosclerotic plaques selectively removed by percutaneous atherectomy. Atherosclerosis (in press)
Dartsch PC, Voisard R, Bauriedel G, Höfling B, Betz E (1990) Growth characteristics and cytoskeletal organization of cultured smooth muscle cells from human primary stenosing and restenosing lesions. Arteriosclerosis 10 (in press)
Eskin SG, Sybers HD, Lester JW, Navarro LT, Gotto AM Jr, DeBakey ME (1981) Human smooth muscle cells cultured from atherosclerotic plaques and uninvolved vessel wall. In Vitro 17:713–718
Gabbiani G, Kocher O, Bloom WS, Vandekerckhove J, Weber K (1984) Actin expression in smooth muscle cells of rat aortic intimal thickening, human atheromatous plaque, and cultured rat aortic media. J Clin Invest 73:148–152
Geer JC, McGill HC, Strong JP (1961) The fine structure of human atherosclerotic lesions. Am J Pathol 38:263–287
Ghidoni JJ, O'Neal RM (1967) Recent advances in molecular pathology. A review: ultrastructure of human atheroma. Exp Mol Pathol 7:378–406
Grünwald J, Haudenschild CC (1984) Intimal injury in vivo activates vascular smooth muscle migration and explant outgrowth in vitro. Arteriosclerosis 4:183–188
Haust MD, More RH, Movat HZ (1960) The role of smooth muscle cells in the fibrogenesis of arteriosclerosis. Am J Pathol 37:377–389
Höfling B, v Pölnitz A, Backa D, v Arnim T, Lauterjung L, Jauch KW, Simpson JB (1988) Percutaneous removal of atheromatous plaques in peripheral arteries. Lancet 1: 384–386
Jaffe EA, Nachman RL, Becker CG, Minick CR (1973) Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest 52:2745–2756
Jaffe EA, Hoyer LW, Nachman RL (1973) Synthesis of antihemophilic factor antigen by cultured human endothelial cells. J Clin Invest 52:2757–2764
Kocher O, Gabbiani G (1986) Cytoskeletal features of normal and atheromatous human arterial smooth muscle cells. Hum Pathol 17:875–880
Krushinsky AW, Orekhov AN, Smirnov VN (1983) Stellate cells in the intima of human aorta: application of alkaline dissociation method in the analysis of the vessel wall cellular content. Acta Anat 117:266–269
Moss N, Benditt EP (1975) Human atherosclerotic plaque cells and leiomyoma cells. Comparison of in vitro growth characteristics. Am J Pathol 78:175–190
Orekhov AN, Kosykh VA, Repin VS, Smirnov VN (1983) Cell proliferation in normal and atherosclerotic human aorta. II. Autoradiographic observation on deoxyribonucleic acid synthesis in primary culture. Lab Invest 48:749–754
Orekhov AN, Karpova II, Tertov VV, Rudchenko SA, Andreeva ER, Krushinsky AV, Smirnov VN (1984) Cellular composition of atherosclerotic and uninvolved human aorta subendothelial intima. Light-microscopic study of dissociated aortic cells. Am J Pathol 115:17–24
Orekhov AN, Krushinsky AV, Andreeva ER, Repin VS, Smirnov VN (1986) Adult human aortic cells in primary culture: heterogeneity in shape. Heart Vessels 2:193–201
Osborn M, Caselitz J, Püschel K, Weber K (1987) Intermediate filament expression in human vascular smooth muscle and in arteriosclerotic plaques. Virchows Arch A 411: 449–458
Ross R (1986) The pathogenesis of atherosclerosis—an update. N Engl J Med 314:488–500
Ross R, Glomset JA (1973) Atherosclerosis and the arterial smooth muscle cell. Science 180:1332–1339
Ross R, Wight TN, Strandness E, Thiele B (1984) Human atherosclerosis: I. Cell constitution and characteristics of advanced lesions of the superficial femoral artery. Am J Pathol 114:79–93
Schwartz SM, Campbell GR, Campbell JH (1986) Replication of smooth muscle cells in vascular disease. Circ Res 58:427–444
Simpson JB, Selmon JR, Robertson GC, Cipriano PR, Hayden WG, Johnson DE, Fogarty TJ (1988) Transluminal atherectomy for occlusive peripheral vascular disease. Am J Cardiol 61:96G-101G
Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G (1986) A monoclonal antibody against α-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol 103:2787–2796
Thornton SC, Mueller SN, Levine EM (1983) Human endothelial cells: use of heparin in cloning and long-term serial cultivation. Science 222:623–625
Wagner DD, Olmsted JB, Marder VJ (1982) Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells. J Cell Biol 95:355–360
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Dartsch, P.C., Voisard, R. & Betz, E. In vitro growth characteristics of human atherosclerotic plaque cells: Comparison of cells from primary stenosing and restenosing lesions of peripheral and coronary arteries. Res. Exp. Med. 190, 77–87 (1990). https://doi.org/10.1007/PL00020009
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DOI: https://doi.org/10.1007/PL00020009