Increased expression of mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type 2 in human atria during atrial fibrillation.
BACKGROUND
Atrialfibrillation (AF) is associated with the activation of the renin-angiotensin-aldosterone system in the atria. It is not clear whether the expression of a mineralocorticoid receptor (MR), or 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2), conferring aldosterone specificity to the MR, in patients with AF is altered.


OBJECTIVE
Patients with AF may be associated with increased expression of MR and 11betaHSD2 in the atria.


METHODS
Atrial tissue samples of 25 patients with rheumatic heart valve disease undergoing a valve replacement operation were examined. A total of 13 patients had chronic persistent AF (>6 mo) and 12 patients had no history of AF. The MR and 11betaHSD2 expression were analyzed at the mRNA and protein level. The localization of MR and 11betaHSD2 in atrial tissue was performed using specific immunohistochemistry staining.


RESULTS
The results of real-time quantitative polymerase chain reaction (PCR) showed that AF groups, in comparison with sinus rhythm, had a higher mRNA expression level of MR or 11betaHSD2 (all P < 0.01). Both the MR and 11betaHSD2 protein expression level in atrial tissue were also significantly increased in patients with AF compared with patients with sinus rhythm (P < 0.05 or P < 0.01). The immunohistochemical staining of MR or 11betaHSD2 demonstrated that MR and 11betaHSD2 predominately located in the cytoplasm of myocardial cells in the atrium and the intensity and density of immunostaining appeared to be increased in the atria of patients with AF compared to those without AF.


CONCLUSIONS
Increasing expression of MR and 11betaHSD2 in the atria during AF is one of the molecular mechanisms for development of atrial interstitial fibrosis in patients with AF. These findings may have an important impact on the treatment of AF with aldosterone antagonists.
De-An
Pei
P
Division of Cardiology, Hangzhou Red Cross Hospital, Hangzhou, China. smmu.peidean@126.com
Li
Li
L
Zhi-Yun
Xu
X
Jin-Yu
Huang
H
Zheng-Ming
Xu
X
Min
Wang
W
Qiang
Yao
Y
Shi-Eng
Huang
H
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000096:biosynthesis* / Q000378:metabolism; D000328:Adult; D001281:Atrial Fibrillation / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D005355:Fibrosis; D006325:Heart Atria / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger / Q000096:biosynthesis; D018161:Receptors, Mineralocorticoid / Q000096:biosynthesis* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D012214:Rheumatic Heart Disease / Q000150:complications
D000451:Mineralocorticoid Receptor Antagonists; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2