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Platelets and Thrombosis in the Development of Atherosclerosis and Its Complications

  • J. F. Mustard
  • M. A. Packham
  • R. L. Kinlough-Rathbone
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 102)

Abstract

Platelets, blood flow, and endothelial injury are among the factors that determine the sites at which atherosclerosis develops. Smooth muscle cells in the vessel wall proliferate in response to endothelial injury;and in addition, endothelial injury plays a role in the development of mural and occlusive thrombi in major arteries and thereby contributes to the development of clinical complications of atherosclerosis. Factors that cause endothelial injury therefore appear to be involved both in the development of atherosclerosis and in its thromboembolic complications. Platelets appear to have a key role in both processes. In animal experiments, platelets that adhere to the subendothelium release a factor which stimulates smooth muscle cell proliferation. In addition, platelets that interact with the damaged vessel wall release factors that result in further accumulation of platelets at an injury site, and also accelerate the coagulation process. Recently it has been shown that repeated endothelial injury produces a surface on the vessel wall that is more thrombogenic than that produced by a single injury, and also results in the accumulation of proteoglycans in the vessel wall. Proteoglycans may trap lipoproteins and thus promote their accumulation at sites of endothelial injury. Injury itself leads to increased permeability of the vessel wall to plasma proteins.

Our increased understanding of the pathways involved in these processes has made it possible to examine the effects of smoking, diet, and drugs on the process. Smoking and diet may damage the endothelium, thereby influencing the development of atherosclerosis and its thromboembolic complications. There are three possible ways of detecting changes in the endothelium: 1) by measuring platelet survival, because in some animals damage to the endothelium is associated with shortened platelet survival; 2) by assaying materials released from the platelets into the circulation; and 3) by examining the blood for platelets that have undergone a release reaction. The detection of altered platelets could be used as an indicator of vessel injury or thromboembolism.

A number of drugs that modify platelet function are now being tested for their effects on these reactions. In animals, drugs such as aspirin or sulfinpyrazone do not appear to inhibit platelet adherence to the subendothelium or release of constituents from platelets adhering to collagen. Thus, it is not surprising that these drugs seem to have little effect on the proliferative response of the vessel wall to endothelial injury. Nevertheless, other effects of these drugs may be important in modifying the thromboembolic complications of vessel wall damage. The results of clinical trials now underway may indicate whether modifying platelet function can significantly influence the clinical complications of atherosclerosis.

Keywords

Vessel Wall Endothelial Injury Smooth Muscle Cell Proliferation Platelet Factor Mural Thrombus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1978

Authors and Affiliations

  • J. F. Mustard
    • 1
    • 2
  • M. A. Packham
    • 1
    • 2
  • R. L. Kinlough-Rathbone
    • 1
    • 2
  1. 1.Department of PathologyMcMaster UniversityHamiltonCanada
  2. 2.Department of BiochemistryUniversity of TorontoTorontoCanada

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