Suppressed expression of GTP cyclohydrolase I mRNA and accelerated expression of inducible nitric oxide synthase mRNA in endomyocardial biopsy specimens from patients with dilated cardiomyopathy

Clin Chim Acta. 2005 Mar;353(1-2):103-7. doi: 10.1016/j.cccn.2004.10.004.

Abstract

Background: Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase, and GTP cyclohydrolase I (GCHI) is a rate-limiting enzyme in the biosynthesis of BH4. The expression of inducible nitric oxide synthase (iNOS) was earlier demonstrated in the ventricles of patients with dilated cardiomyopathy (DCM) although that of GCHI was not clarified. The present study was designed to determine the GCHI mRNA expression as well as to confirm iNOS mRNA expression in endomyocardial biopsy specimens from patients with DCM.

Methods: Clinical details were assessed in 19 patients with DCM and in 9 control subjects. The real-time reverse transcription polymerase chain reaction (PCR) was performed on total RNA extracted from endomyocardial biopsy specimens. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA was quantified for use as an internal control.

Results: iNOS/GAPDH for the DCM samples was 4.8-fold greater than that for the control ones (P<0.01), whereas the GCHI/GAPDH for the DCM samples was reduced to 31.1% of the control (P<0.05).

Conclusions: The increased expression of iNOS mRNA was confirmed in endomyocardial biopsy specimens from patients with DCM. The GCHI mRNA level was suppressed in these specimens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Biopsy
  • Cardiomyopathy, Dilated / enzymology*
  • Cardiomyopathy, Dilated / pathology
  • Case-Control Studies
  • DNA Primers
  • GTP Cyclohydrolase / genetics*
  • Humans
  • Myocardium / pathology*
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase Type II
  • RNA, Messenger / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA Primers
  • RNA, Messenger
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • GTP Cyclohydrolase