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.
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.
Ohtsuki
Masatsugu
M
Department of Internal Medicine, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan. mohtsuki@fujita-hu.ac.jp
Nomura
Takahide
T
Morimoto
Shin-ichiro
S
Hiramitsu
Shinya
S
Uemura
Akihisa
A
Kato
Shigeru
S
Kato
Yasuchika
Y
Shiraishi
Hiroaki
H
Shimokubo
Junko
J
Yamamoto
Naoki
N
Hishida
Hitoshi
H
D001483:Base Sequence; D001706:Biopsy; D002311:Cardiomyopathy, Dilated / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D017931:DNA Primers; D006136:GTP Cyclohydrolase / Q000235:genetics*; D006801:Humans; D009206:Myocardium / Q000473:pathology*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D012333:RNA, Messenger; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D006136:GTP Cyclohydrolase