mRNA expression of inducible nitric oxide synthase, endothelial nitric oxide synthase and vascular endothelial growth factor in esophageal mucosa biopsy specimens from patients with reflux esophagitis.
OBJECTIVE
Nitric oxide (NO) production is elevated in the intestine and may contribute to intestinal injury during inflammation. However, how the expression of inducible NO synthase (iNOS) mRNA and endothelial NO synthase (eNOS) mRNA in the esophageal mucosa contribute to mucosal damage caused by reflux esophagitis remains unknown. Since vascular endothelial growth factor (VEGF) exerts its action on microcirculation, contributing to angiogenesis and inflammation, we examined the role of VEGF together with iNOS and eNOS on development of reflux esophagitis.


METHODS
The mRNA expression levels of iNOS, eNOS and VEGF were measured in biopsy specimens from 25 patients with reflux esophagitis, using TaqMan PCR and reverse transcription PCR.


RESULTS
The expression of iNOS mRNA in the esophageal mucosa increased parallel to the severity of the esophagitis. There were no significant differences between both eNOS and VEGF mRNA expression levels and the severity of the esophagitis. The existence of gastric mucosal atrophy, hiatus hernia, therapy and Helicobacter pylori infection did not affect the levels of mRNA expression.


CONCLUSIONS
The accumulation of NO, produced by iNOS, was considered to be related to the exacerbation of reflux esophagitis. Therapeutic intervention that reduces NO production may thus be of use in preventing development of esophageal mucosal injury in patients with reflux esophagitis.
Inamori
Masahiko
M
Third Department of Internal Medicine, Yokohama City University, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. inamorim@med.yokohama-cu.ac.jp
Shimamura
Takeshi
T
Nagase
Hajime
H
Abe
Yasunobu
Y
Umezawa
Tadashi
T
Nakajima
Atsushi
A
Saito
Toshifumi
T
Ueno
Norio
N
Tanaka
Katsuaki
K
Sekihara
Hisahiko
H
Togawa
Jun-ichi
J
Kaifu
Hiroki
H
Tsuboi
Hideo
H
Kayama
Hideyuki
H
Tominaga
Shizuo
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D004942:Esophagitis, Peptic / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III