Gene expression in distinct regions of the heart.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read Online Read More Add to Saved list
  • Author(s): Thum, Thomas; Borlak, Jurgen
  • Source:
    Lancet. 3/18/2000, Vol. 355 Issue 9208, p979. 5p. 2 Black and White Photographs, 3 Charts, 2 Graphs.
  • Additional Information
    • Subject Terms:
      HEART abnormalities; GENE expression; CYTOCHROME P-450; MONOOXYGENASES; GENETICS
    • Abstract:
      SummaryBackground: Cytochrome P450 mono-oxygenases bring about metabolism of many drugs, including verapamil, but no information is available on the metabolism of such drugs in the human heart.Methods: We investigated the gene expression of major human cytochrome P450 mono-oxygenases in the various regions of explanted hearts from six patients with dilated cardiomyopathy and one with transposition of the arterial trunk. For comparison we also studied samples of liver and lung from three patients and two samples of normal heart. The biological significance of tissue-specific cytochrome mono-oxygenase gene expression was further investigated by study of the microsomal metabolism of verapamil in ventricular tissue.Findings: mRNA for the cytochromes 1A1, 2B6/7, 2C8-19, 2D6, and 4B1 was predominantly expressed in the right ventricle; the unilateral expression of the 2D6 gene in right- venticular tissue is important because of its key role in the metabolism of Beta-blockers. A strong correlation between tissue-specific gene expression and enzyme activity was found; microsomal metabolism of verapamil was confined to the right ventricle. By contrast, cytochrome P450 3A genes (which are the major drug-metabolising enzymes in the liver and the lung) were not expressed in any of the human heart tissues, and mRNA transcripts for epoxide hydrolase, cytochrome P450 2E1, and flavin-containing mono-oxygenases 2 and 5 were detected in all regions of the human heart and the great vessels.Interpretation: These findings show that expression of genes for cytochrome P450 mono-oxygenases and verapamil metabolism are found predominantly in the right side of the heart. This finding may explain lack of efficacy of certain cardioselective drugs. [ABSTRACT FROM AUTHOR]
    • Abstract:
      Copyright of Lancet is the property of Lancet and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)