Atrial expression of endothelial nitric oxide synthase in patients with and without atrial fibrillation.
BACKGROUND
Atrial fibrillation (AF) is associated with oxidative stress within the fibrillating atrial myocardium. Experimental studies suggest that reduced levels of nitric oxide (NO) caused by down-regulation of the NO synthase (eNOS) contribute to the development of prothrombotic endocardial remodeling in AF. This study was designed to determine the endocardial expression of eNOS in atrial tissue samples from patients with and without AF.


METHODS
Tissue microarrays were used to analyze right atrial tissue specimens obtained from 234 patients (38 with AF; 196 with sinus rhythm) for differences in atrial eNOS expression. In selected patients, immunohistological results were confirmed by Western blotting.


RESULTS
Immunohistochemical analyses showed that eNOS is expressed by endocardial cells and myocytes. However, endocardial expression of eNOS was not independently related to AF per se. There was no difference between paroxysmal and persistent AF. Clinical factors like gender (P=.05) and coronary artery disease (P=.06) were associated with down-regulation of eNOS. Interestingly, diabetes mellitus (P=.02) was associated with an up-regulation of endocardial eNOS, whereas other risk factors for thromboembolic events did not influence eNOS levels. Multivariable analysis showed that eNOS expression is influenced by interactions between diabetes mellitus and AF (P=.09) as well as by interactions between gender and AF (P=.04). Lowest levels of eNOS were found in women with AF.


CONCLUSIONS
AF does not independently effect atrial eNOS expression in humans. Due to the nonuniform regulation of endocardial eNOS expression, it appears unlikely that down-regulation of eNOS is a final common pathway for the development of prothrombotic endocardial remodeling, since classical risk factors for thromboembolic events do not reduce endocardial eNOS protein.
Bukowska
Alicja
A
Institute of Experimental Internal Medicine, University Hospital Magdeburg, Magdeburg, Germany.
Röcken
Christoph
C
Erxleben
Michaela
M
Röhl
Friedrich-Wilhelm
FW
Hammwöhner
Matthias
M
Huth
Christof
C
Ebert
Matthias P A
MP
Lendeckel
Uwe
U
Goette
Andreas
A
D000368:Aged; D001281:Atrial Fibrillation / Q000201:enzymology*; D015153:Blotting, Western; D003920:Diabetes Mellitus / Q000201:enzymology; D004699:Endocardium / Q000201:enzymology; D004730:Endothelium, Vascular / Q000201:enzymology; D005260:Female; D006325:Heart Atria / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D046888:Tissue Array Analysis
D052250:Nitric Oxide Synthase Type III