Summary
In rabbit carotid arteries arteriosclerotic lesions were induced by repeated local transmural electrical stimulations. The sequence of early morphological alterations in the vessel wall and especially the kinetics of leukocytes were examined by transmission electron microscopy.
After a stimulation period of only 1 day monocytes and heterophilic granulocytes adhered to the endothelial surface. In the subendothelium mainly beneath the anode, focal amorphous insudates were present together with mononuclear and granulocytic cells. Thereby, the endothelium was maintained as a continuous lining as shown by surface staining with silver nitrate. However, both pattern and size of the endothelial cells were altered in comparison to the controls. Some of the endothelial cells displayed a heavy cytoplasmic silver salt deposition. After 2 days of the electrical stimulation schedule, the first myocytes occurred in the subendothelial space. The mediamyocytes sending pseudopods through the internal elastic lamina still appeared to be in a contractile phenotype. In the 7-day-old proliferative lesion modulated smooth muscle cells were the predominant cell type; only 10%–20% of the subendothelial cells were identified as macrophages and heterophils. This proportion decreased further, and after a stimulation period of 28 days the granulocytes disappeared completely. At this stage of plaque development, the intimal myocyte population mainly consisted of contractile smooth muscle cells and intermediary states between the contractile and modulated phenotype.
The insudation, immigration of white blood cells, and subsequent migration and proliferation of myocytes reinforces the view that the initial phases of arteriosclerotic lesions may represent a special form of an inflammatory response.
Similar content being viewed by others
References
Apfel H, Betz E (1985) Der elektrische Widerstand von Arterienwänden bei Atheromentwicklung. Angio Archiv 7:91–93
Betz E, Hämmerle H, Strohschneider T (1985) Inhibition of smooth muscle cell proliferation and endothelial permeability with Flunarizine in vitro and in experimental atheromas. Res Exp Med (Berl) 185:325–340
Betz E, Schlote W (1979) Responses of vessel walls to chronically applied electrical stimuli. Basic Res Cardiol 74:10–20
Eitel W, Schmid G, Schlote W, Betz E (1980) Early arteriosclerotic changes of the carotid artery wall induced by electrostimulation. A study by scanning and transmission electron microscopy. Pathol Res Pract 170:211–229
Faggiotto A, Ross R, Harker E (1984) Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation. Arteriosclerosis 4:323–340
Faggiotto A, Ross R (1984) Studies of hypercholesterolemia in the nonhuman primate. II. Fatty streak conversion to fibrous plaque. Arteriosclerosis 4:341–356
Faustmann PM, Dermietzel R (1985) Extravasation of polymorphonuclear leukocytes from the cerebral microvasculature. Inflammatory response induced by alpha-bungarotoxin. Cell Tissue Res 242:399–407
Gerrity RG (1981a) The role of the monocyte in atherogenesis. I. Transition of bloodborne monocytes into foam cells in fatty lesions. Am J Pathol 103:181–190
Gerrity RG (1981b) The role of the monocyte in atherogenesis. II. Migration of foam cells from atherosclerotic lesions. Am J Pathol 103:191–200
Glenn KC, Ross R (1981) Human monocyte-derived growth factor(s) for mesenchymal cells: activation of secretion by endotoxin and concanavalin A. Cell 25:603–615
Grotendorst GR, Seppa HE, Kleinmann HK, Martin GR (1981) Attachment of smooth muscle cells to collagen and their migration toward platelet-derived growth factor. Proc Natl Acad Sci USA 78:3669–3672
Hansson GK (1985) Injury and death of endothelial cells in vivo and in vitro. Blick — Innere Med 7:9 [Abstr]
Hansson GK (1980) Endothelial injury and monocyte adhesion in atherogenesis. Experimental studies in the rabbit. Doctoral thesis, University of Göteborg, Göteborg
Hansson GK, Björnheden T, Bylock A, Bondjers G (1981) Fc-dependent binding of monocytes to areas with endothelial injury in the rabbit aorta. Exp Mol Pathol 34:264–280
Haudenschild C, Studer A (1971) Early interactions between blood cells and severely damaged rabbit aorta. Eur J Clin Invest 2:1–7
Joris J, Majno G (1979) Inflammatory components of atherosclerosis. In: Weissmann G, Samuelsson B, Paoletti R (eds) Advances in inflammation research, vol 1. Raven Press, New York, p 71
Joris J, Zand T, Nunnari JJ, Krolikowski FJ, Majno G (1983) Studies on the pathogenesis of atherosclerosis. I. Adhesion and emigration of mononuclear cells in the aorta of hypercholesterolemic rats. Am J Pathol 113:341–358
Reidy MA, Schwartz SM (1984) Recent advances in molecular pathology. Arterial endothelium — assessment of in vivo injury. Exp Mol Pathol 41:419–434
Ross R (1986) The pathogenesis of atherosclerosis — an update. N Engl J Med 314:488–500
Schwartz CJ, Sprague EA, Kelly JL, Valente AJ, Suenram CA (1985) Aortic intimal monocyte recruitment in the normo and hypercholesterolemic baboon(Papio cynocephalus). An ultrastructural study: Implications in atherogenesis. Virchows Arch [Pathol Anat] 405:175–191
Trillo AA (1982) The cell population of aortic fatty streaks in African green monkey with special reference to granulocytic cells. An ultrastructural study. Atherosclerosis 43:253–275
Viele D, Betz E (1985) Effect of the calcium entry blocker, Flunarizine on ruthenium red uptake by endothelial cells following acute electrical stimulation of rabbit carotid arteries. Basic Res Cardiol 80:58–65
Zand T, Underwood JM, Nunnari JJ, Majno G, Joris I (1982) Endothelium and “silver lines”. An electron-microscopic study. Virchows Arch [Pathol Anat] 395:133–144
Zinner G, Gotlieb R (1961) Weitere Beobachtungen zur pathologischen Histologie der Venenendothelien. Virchows Arch [Pathol Anat] 334:337–341
Author information
Authors and Affiliations
Additional information
Supported by DFG BE 324/14-1
Rights and permissions
About this article
Cite this article
Kling, D., Holzschuh, T. & Betz, E. Temporal sequence of morphological alterations in artery walls during experimental atherogenesis — occurrence of leukocytes. Res. Exp. Med. 187, 237–250 (1987). https://doi.org/10.1007/BF01852050
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01852050