A dynamic pathology of atherosclerosis

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Abstract

Currently available evidence indicates that atherosclerosis of large and medium arteries is associated with the influx and trapping of low-density plasma lipoprotein within the myointimal and medial cells of the arterial wall. Many factors, including hyperlipemia, hemodynamic arterial injury and hypoxia, hasten and facilitate this process, but too little is known of the factors and mechanisms responsible. The role of local platelet aggregation in initiating localized vascular injury and increased vascular permeability is yet to be fully clarified.

Blood vessels can no longer be viewed as mere blood conduits. They are composed mainly of actively metabolizing smooth muscle cells, which have a wide range of metabolic potentialities, summarized diagrammatically in Figure 6. An understanding of the metabolism of these cells is central for an appreciation of the pathogenesis of atherosclerosis for it is within these cells that low-density lipoprotein is first entrapped and accumulates. These cells, especially in the deeper layers of the inner media, exist on the brink of hypoxia and are therefore particularly susceptible to a variety of noxious stimuli. The exact identity of the factors responsible for the initiation of a particular smooth muscle cell response to injury remains unknown. However, from the experimental evidence of the characteristic smooth muscle cell response to various food fats it seems likely that certain components of the low-density lipoproteins in appropriate experimental animals elicit the typical vascular response associated with the feeding of a given food fat. Identification of the lipoprotein components important for the development of a particular cellular reaction pattern is a major problem in atherosclerosis research.

A thorough study of the enzymatic potentialities and responses of smooth muscle cells is necessary for at least three reasons:

  • 1.

    (1) Detailed knowledge of the metabolic characteristics of these cells will be provided.

  • 2.

    (2) Such studies may also uncover a suitable quantitative measure of the incipient atherosclerotic process—a measure which would be most useful for experimental elucidation of the early pathogenesis of this disease.

  • 3.

    (3) It is through such studies that we can hope to gain a better appreciation of the potentialities for dealing with this serious health hazard.

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    That part of the investigative work which was carried out in this laboratory and summarized in this manuscript was supported by grant PHS-HE6894.

    1

    From the Department of Pathology, University of Chicago, Chicago, Illinois 60637.

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