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Proliferation versus atrophy — the ambivalent role of smooth muscle cells in human atherosclerosis

  • Conference paper
Arteriosclerosis

Summary

Most of the current concepts on morphogenesis of atherosclerosis attribute the development of atherosclerotic lesions to the combined effects of two main cellular events: 1) activation of macrophages leading to lipoprotein phagocytosis by scavenger cells, and 2) proliferation of smooth muscle cells (SMC). SMC-like cells producing collagenous fibers and extracellular matrix are particularly involved in the formation of the so-called fibrous caps surrounding the core of an atheroma composed of foam cells and fatty debris. The fiber-forming SMC, in general, are said to result from a proliferation of media SMC which once have moved into the intima.

This view of origin of the fiber-forming SMC and the alleged proliferation of media SMC is mainly derived from experimental assays exposing the vessel wall to various kinds of physical or chemical injuries. It is the purpose of this paper to demonstrate that the results of those more or less ephemeral experiments differ from findings obtained from a combined histochemical and morphometric analysis of SMC in the aortic media in spontaneous human arteriosclerosis.

Instead of any proliferation, a significant atrophy of SMC occurs in the media with advancing age and progress of atherosclerosis. To some extent, this decrease in numerical and volumetric density of SMC is accompanied with intra- and extracellular calcification. It seems likely that the loss of contractile capacity of the media resulting from wasting of SMC, does slow down the stream of the interstitial fluid in the arterial wall. This stagnation must increase the life span of LDL moving through the interstitial space. The chemical alteration ensuing from aging of LDL mediates its binding to the scavenger receptors and uptake by macrophages.

So far, muscular atrophy of the media forms an atherogenic factor of its own, leading to final results similar to those as known from conditions of intravascular aging of LDL in hyperlipoproteinemia. The augmentation of SMC-like cells in the intima is hardly to be derived from the atrophic media, but rather seems to be due to local proliferation of cells which, in the normal state, do occur in small numbers in the subendothelial space. These so-called myointimal or Langhans-cells share with SMC their content of α-actin, but they differ by their stellate configuration from the bipolar shape SMC of the media.

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Authors and Affiliations

  1. Department of Pathology, University of Freiburg, Germany

    Prof. Dr. med. H.-E. Schaefer

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  1. Prof. Dr. med. H.-E. Schaefer
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  1. Abt. Innere Medizin III, Medizinische Universitätsklinik, Hugstetter Straße 55, 79106, Freiburg, Deutschland

    H. Just  & A. M. Zeiher  & 

  2. Pathologisches Institut, Heinrich-Heine-Universität, Moorenstraße 5, 40225, Düsseldorf, Deutschland

    W. Hort

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© 1994 Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt

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Schaefer, HE. (1994). Proliferation versus atrophy — the ambivalent role of smooth muscle cells in human atherosclerosis. In: Just, H., Hort, W., Zeiher, A.M. (eds) Arteriosclerosis. Steinkopff. https://doi.org/10.1007/978-3-642-85660-0_5

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  • DOI: https://doi.org/10.1007/978-3-642-85660-0_5

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  • Print ISBN: 978-3-642-85662-4

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