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. CONCLUSION: 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. Copyright 2010 Elsevier Inc. All rights reserved.
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. CONCLUSION: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. Copyright 2010 Elsevier Inc. All rights reserved.
Authors: Andreas Goette; Jonathan M Kalman; Luis Aguinaga; Joseph Akar; Jose Angel Cabrera; Shih Ann Chen; Sumeet S Chugh; Domenico Corradi; Andre D'Avila; Dobromir Dobrev; Guilherme Fenelon; Mario Gonzalez; Stephane N Hatem; Robert Helm; Gerhard Hindricks; Siew Yen Ho; Brian Hoit; Jose Jalife; Young-Hoon Kim; Gregory Y H Lip; Chang-Sheng Ma; Gregory M Marcus; Katherine Murray; Akihiko Nogami; Prashanthan Sanders; William Uribe; David R Van Wagoner; Stanley Nattel Journal: Heart Rhythm Date: 2016-06-10 Impact factor: 6.343
Authors: Andreas Goette; Jonathan M Kalman; Luis Aguinaga; Joseph Akar; Jose Angel Cabrera; Shih Ann Chen; Sumeet S Chugh; Domenico Corradi; Andre D'Avila; Dobromir Dobrev; Guilherme Fenelon; Mario Gonzalez; Stephane N Hatem; Robert Helm; Gerhard Hindricks; Siew Yen Ho; Brian Hoit; Jose Jalife; Young-Hoon Kim; Gregory Y H Lip; Chang-Sheng Ma; Gregory M Marcus; Katherine Murray; Akihiko Nogami; Prashanthan Sanders; William Uribe; David R Van Wagoner; Stanley Nattel Journal: J Arrhythm Date: 2016-07-11
Authors: Nimrat Grewal; Adriana C Gittenberger-de Groot; Jan H Lindeman; Arthur Klautz; Antoine Driessen; Robert J M Klautz; Robert E Poelmann Journal: Ann Cardiothorac Surg Date: 2022-07
Authors: N Grewal; M C DeRuiter; M R M Jongbloed; M J Goumans; R J M Klautz; R E Poelmann; A C Gittenberger-de Groot Journal: Neth Heart J Date: 2014-09 Impact factor: 2.380