| Objectives The purpose of this study was to determine whether atrial expression of the angiotensin-converting enzyme (ACE), the angiotensin II type 1 and type 2 receptors (ATpR, AIVR), collagen I, collagne III and of the isoforms of transforming growth factor-beta (TGF-P) is altered in patients with rheumatic heart disease and atrial fibrillation.Methods and Results In the first portion of the study, atrial tissue samples (100mg) of 52 patients undergoing valve replacement surgery were examined. 22 patients had no history of AF, 9 patients had paroxysmal AF (<6 months PAF) and 21 patients with chronic persistent AF( 6 months CAF). Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction(PCR) the cDNA of interest genes and of glyceraldehydes-3-phosphate dehydrogenase(GAPDH) were coamplified and separated by ethidium bromide stained gel-electrophoresis. The levels of mRNA expression were quantified by densitometry. The amount of ACE mRNA was significantly increased in patients with CAF (0.82 0.33 vs 0.56 0.18, p<0.01) and in patients with PAF (0.76 0.22 vs 0.56 0.18, p<0.05) compared to patients with sinus rhythm. No differences between CAF and PAF were found. The amount of AT2-R mRNA was significantly increased in patients with CAF (0.85 0.32; n=21) compared to patients with sinus rhythm(0.64 0.24; n=22; p<0.05). The differences in ATi-R mRNA levels between patients with PAF and patients with sinus rhythm did not reach statistical significance (0.64 0.24 vs 0.6610.34 p>0.05). The AT1-R mRNA content was similar in all groups. No correlation was found between the mRNA content of ACE and of AT2-R and the baseline characteristics of patients underlying the study such as gender, age, previous duration of AF, left atrial diameter, right atrial diameter, left ventricular ejection fraction and the valvular involved. In the second part of this study, A total of 49 patients with rheumatic heart disease were included. 20 patients had no history of AF, 8 patients had paroxysmalAF (PAF) and 21 patients with chronic persistent AF( 6 months, CAF). Atrial tissue was obtained from the right atrial appendage during valve replacement surgery. Total RNA was isolated and reversely transcribed into cDNA. In a semi-quantitative polymerase chain reaction the cDNA of interest genes and of the housekeeping gene 3 -actin were coamplified and separated on an agarose gel by electrophoresis and stained with ethidium bromide. The levels of mRNA expression were quantified by densitometry. The mRNA amounts of collagen I and collagen III were significantly increased in atrial tissue of patients with CAF (collagen I: 1.04 0.33; collagen III: 1.28 0.46; n=20; p<0.001) as well as PAF (n=8; collagen I: 0.93 0.34, p<0.001; collagen III: 1.12 0.17, p<0.05) compared to patients in sinus rhythm (collagen I: 0.68 0.23; collagen III: 0.86 0.42; n=21) . The differences between CAF and PAF were not significant. Compared with patients with sinus rhythm, the expression of TGF- 1 was significantly increased in patients with CAF (1.04 0.27 vs 0.69 0.42, p<0.001) and increased in patients with PAF (0.95 0.21 vs 0.69 0.42, p<0.05) . No significant differences between CAF and PAF were found. The TGF-p2 mRNA content was similar in all groups. There were no correlation between age and the mRNA content of collagen I, collagen III and TCP- 1.Conclusions The up-regulation of ACE mRNA may have correlation with the initiation or maintenance of AF, and may be one of underlying mechanism that the ACEI reduced the incidence of AF. The increase of AT2-R may be compensatory to inhibit the progression of angiotensin II-dependent interstitial fibrosis. The up-regulation of collagen I, Collagen III, TCP- 1 mRNA in human atrium may have correlation with the initiation or maintenance of AF, and may contribute to a molecular mechanism for the development of atrial fibrosis in patients with rheumatic heart disease which produces a substrate for AF.
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