GATA5 and endothelial nitric oxide synthase expression in the ascending aorta is related to aortic size and valve morphology.
BACKGROUND
The pathogenesis of aortic dilatation in patients with congenital aortic valve anomalies is poorly understood. Recent studies suggest that alterations of gene expression may be related to ascending aortic aneurysm formation in these patients. Knockout of endothelial nitric oxide synthase (eNOS) and GATA5 is associated with bicuspid aortic valves in mice. To study the role of eNOS and GATA5 in human congenital aortic valve disease and aortic dilatation, we investigated their gene expression in aortic tissue from patients with unicuspid, bicuspid, and tricuspid aortic valves.


METHODS
Samples from 84 patients (33 tricuspid, 32 bicuspid, and 19 unicuspid) were harvested intraoperatively from the ascending aorta. GATA5 and eNOS expression was determined by real-time polymerase chain reaction.


RESULTS
GATA5 and eNOS expression in the aortic wall from patients with unicuspid aortic valves (GATA5: mean [M], 2.14; standard deviation [SD], 1.72; eNOS: M, 3.40; SD, 3.83) was significantly higher than in tricuspid aortic valves (GATA5: M, 1.12; SD, 0.80; eNOS: M, 1.00; SD, 0.74; each p < 0.05). Patients with bicuspid aortic valves (GATA5: M, 1.29, SD, 1.33; eNOS: M, 1.66; SD, 1.31) had a significantly higher eNOS expression than patients with tricuspid aortic valves (p < 0.05). The expression levels of eNOS and GATA5 correlated positively with each other and negatively with the ascending aortic diameter.


CONCLUSIONS
Our data suggest that GATA5, possibly through upregulation of eNOS, plays a role in the development of aortic dilatation in patients with unicuspid and bicuspid aortic valves. The differential gene expression in patients with unicuspid compared with bicuspid aortic valves suggests that the pathogenesis of both aortic valve anomalies may be different.
Department of Thoracic and Cardiovascular Surgery, Saarland University Medical Center, Homburg/Saar, Germany. Electronic address: dominichenn@fastmail.jp.
Dominic
D
Henn
Department of Thoracic and Cardiovascular Surgery, Saarland University Medical Center, Homburg/Saar, Germany.
Hilja
H
Perttunen
Department of Thoracic and Cardiovascular Surgery, Saarland University Medical Center, Homburg/Saar, Germany.
Simon
S
Gauer
Department of Thoracic and Cardiovascular Surgery, Saarland University Medical Center, Homburg/Saar, Germany.
Wolfram
W
Schmied
Department of Cardiovascular Surgery, Hospital Virgen de la Victoria, Campus de Teatinos, Málaga, Spain.
Carlos
C
Porras
Department of Cardiovascular Surgery, Hospital Virgen de la Victoria, Campus de Teatinos, Málaga, Spain.
Miguel
M
Such
Department of Thoracic and Cardiovascular Surgery, Saarland University Medical Center, Homburg/Saar, Germany.
Hans-Joachim
HJ
Schäfers
D000328:Adult; D000368:Aged; D001011:Aorta / Q000378:metabolism / Q000473:pathology*; D001021:Aortic Valve / Q000473:pathology*; D005260:Female; D050992:GATA5 Transcription Factor / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis
D050992:GATA5 Transcription Factor; C494755:GATA5 protein, human; D012333:RNA, Messenger; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III