[The relation between angiotensin II receptors 1 and 2, and CYP11B2 and atrial structural remodeling in patients with atrial fibrillation].
OBJECTIVE
To investigate the relation between of the angiotensin II receptors 1 and 2 (AT1-R and AT2-R), and aldosterone (Ald) synthetase CYP11B2 gene expression and atrial structural remodeling.


METHODS
Thirty-eight patients were divided into three groups: sinus rhythm (SR) group (n = 11), paroxysmal atrial fibrillation (pAF) group (n = 13, with a duration of AF < 6 months), and constant atrial fibrillation (cAF) group (n = 14, with a duration of AF > 6 months) and underwent open thoracic surgery. 500 mg of tissue of right appendage was taken during the off-pump operation (tissue of left appendage was also taken in 8 patients of the cAF group). The levels of AT1-R, AT2-R, and CYP11B2 were detected. With semiquantitative polymerase chain reaction. Immunohistochemistry was used to localize AT1-R.


RESULTS
The mean diameter of the left atrium of the cAF group was (5.8 +/- 0.6) cm, significantly greater than those of the pAF and SR groups (4.2 +/- 0.7) cm and (3.3 +/- 0.4) cm respectively, (both P < 0.01). However, there was not significant difference in the mean diameter of left atrium between the pAF and SR groups (P > 0.05). The CYP11B2R mRNA expression of the cAF group was 0.41 +/- 0.03, significantly higher than those of the pAF and SR groups (0.27 +/- 0.09 and 0.23 +/- 0.01 respectively, both P < 0.05). The AT1-R mRN expression level of the cAF group was 1.03 +/- 0.04, significantly lower than that of the SR group (0.90 +/- 0.10, P < 0.05). The AT2-R mRNA expression level of the cAF group was 1.16 +/- 0.16, significantly higher than that of the SR group (0.90 +/- 0.10, P < 0.05). In the SR group the AT1-R protein expression was mainly seen in the cellular membrane of the atrial cardiac muscle cells and rarely seen in the fibroblasts and vascular sooth muscle cells, however, in the pAF group AT1-R positive staining was seen in the cellular membrane, cytoplasm of the atrial cardiac cells, fibroblasts, and vascular sooth muscle cells, and the AT1-R positive staining of the cAF group was stronger than that of the pAF group and weaker then that of the SR group.


CONCLUSIONS
The atrial structural remodeling is mediated by tissue RAS. The downregulation of AT1-R mRNA is probably an excessive reaction of atrial myocardium to tissue Ang II, while the upregulation of AT2-R mRNA is probably an adaptive and compensatory reaction of atrial myocardium to tissue Ang II. The regulation of AT-R may occur at the level of transcription and translation of the protein synthesis. In the cAF and pAF patients, the increase of the gene expression of CYP11B2 shows that Ald may be involved in the pathophysiological process of atrial remodeling in AF.
Wu
Yong-Quan
YQ
Department of Cardiology, Tongji Hospital Affiliated to Tongji University, Shanghai 200065, China.
Wang
Xue-Dong
XD
Fang
Hong
H
Wang
Yong-Liang
YL
Zhang
Yu-Chen
YC
Su
Li-Jie
LJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016275:Atrial Function; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D019405:Cytochrome P-450 CYP11B2