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Homocysteine theory of arteriosclerosis

  • Kilmer S. McCully
    Correspondence
    Address correspondence to Dr. Kilmer S. McCully, Department of Pathology, The Massachusetts General Hospital, Boston, Mass. 02114, U.S.A.
    Affiliations
    Department of Pathology, Harvard Medical School, the James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, Mass., USA

    Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Mass., U.S.A.
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  • Robert B. Wilson
    Footnotes
    Affiliations
    Department of Pathology, Harvard Medical School, the James Homer Wright Pathology Laboratories, Massachusetts General Hospital, Boston, Mass., USA

    Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Mass., U.S.A.
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  • Author Footnotes
    ∗ Present address: School of Veterinary Medicine, University of Missouri, 202 Connaway, Columbia, Mo. 65201, U.S.A.
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      Abstract

      Arteriosclerotic plaques were found in the aorta and arteries of rabbits given homocysteine thiolactone, methionine or homocysteic acid, both parenterally and in a synthetic diet. Animals given large doses of parenteral methionine or homocysteine thiolactone died of pulmonary embolism and pulmonary infarct. Pyridoxine prevented thrombosis and pulmonary embolism but did not prevent arteriosclerotic plaques. These findings and previous work, showing a new metabolic pathway for sulfate ester synthesis from methionine, the somatotrophic activity of homocysteic acid, and control of cellular growth and intercellular matrix synthesis by homocysteine derivatives, suggest a theory to explain aspects of the pathogenesis of arteriosclerosis.

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