Thrombosis and the development of atherosclerosis: Rokitansky revisited

C. J. Schwartz, A. J. Valente, J. L. Kelley, E. A. Sprague, E. H. Edwards

Research output: Contribution to journalReview articlepeer-review

74 Scopus citations


In this article we have reviewed the evidence that implicates the organization and incorporation of mural thrombi as a significant component of atherosclerotic plaque growth in man. It has been emphasized that there is little or no evidence for a pathogenic role for thrombosis in plaque initiation or for the development of fatty streaks. We have suggested that the rapidly progressive category of atherosclerosis in man, as described by DeBakey, may well reflect a heightened propensity for mural or occlusive thrombosis in these patients. A broad spectrum of experimental studies examining the role of thrombosis in atherogenesis had been critically reviewed. These studies have established that experimental thrombi can become transformed into arterial fibrofatty plaques having many of the morphologic features of atherosclerosis. We have provided evidence, however, that the evolution of thrombi to fibrofatty lesions is dependent on the initial composition of the thrombi and that thrombi with a paucity of platelets and consisting predominantly of fibrin result only in fibrous intimal thickenings. The presence of hypercholesterolemia has been shown to influence the transformation of experimental thrombi. In particular, it slows the rate of thrombolysis, enhances the lipid content of the fibrofatty plaques, increases the numbers of macrophage-derived foam cells, and the frequency and extent of lesion calcification. Detailed lipid compositional studies of organizing thrombi in normolipidemic animals have shown that their lipid composition does not evolve toward the profile characteristic of atherosclerotic lesions and that the macrophage uptake of interstitial lipoproteins is probably a necessary component for the full biochemical development of the lesions. Finally, we have identified some, but by no means all, the unresolved problems and have suggested several avenues for future research in the field of thromboatherosclerosis.

Original languageEnglish (US)
Pages (from-to)189-195
Number of pages7
JournalSeminars in Thrombosis and Hemostasis
Issue number2
StatePublished - 1988

ASJC Scopus subject areas

  • Hematology
  • Cardiology and Cardiovascular Medicine


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