LETTER TO THE EDITOR
Reply
Andreas Boldt, MSc,
Jens Garbade, MD,
Jan Fritz Gummert, MD and
Stefan Dhein, MD
University of Leipzig, Heart Center, Cardiovascular Surgery, Strümpellstrasse 19, D-04289 Leipzig, Germany
AndreasBoldt{at}web.de
Atrial fibrillation (AF) is associated with electrical remodeling in the human atria (1), and angiotensin II (AngII) is involved in the process of atrial electrical remodeling (2). Recently, we analyzed the expression of angiotensin II receptor type 1 (AT1) and 2 (AT2) in the human left atrium and were able to show that AF is associated with an up-regulation of AT1 in the human left atrium (3), but not in the human right atrium. Regarding the expression of AT2 in the right atrium, we could show results similar to Goette et al. (4); however, the results were less pronounced than in the study of Goette et al. This might be caused by different patient populations. Furthermore, we could clearly demonstrate that an underlying mitral valve disease (MVD) did not have any significant influences on the expression of AngII receptor subtypes (Fig. 4A to 4D in Boldt et al. [3]). Other possible effects of an underlying MVD were not mentioned in our study.
Goette et al. (4) claimed a direct comparison between left and right atrial tissue in a single patient. For ethical reasons it was not possible to obtain atrial tissue samples of both atria of a single patient, a fact that concerns most of the other study groups. However, an animal model would provide results that may help to understand pathophysiological mechanisms in AF.
In our study (3), we did not assert to use the immunological analysis for quantification. After finding clear histological differences (by visualization) between patients in sinus rhythm (SR) and AF, we quantified the expression of AT1 and AT2 by Western blot techniques. We could detect a significant increase in AF compared to SR in the AT1 expression, but not in the AT2 expression (Fig. 3A [3]). As shown in Figure 2, there was a higher level of AT1 in patients with both lone AF and MVD + AF compared to a lower level in patients with SR. In contrast to the claim of Goette et al., there was no lack of expression of AT1 in SR; however, a low level (Fig. 2 [3]).
We cannot exclude that other substrates or pathways may influence the expression of AT1/AT2 in patients with AF. However, a time-dependent expression of AT1 has not yet been analyzed and is difficult to investigate in humans. In fact, differences exist in the expression of angiotensin II receptor subtypes between human left and right atrium. Furthermore, because AF depends from the left atrium (5), it is important to consider both atria to draw possible conclusions about pathophysiological influences of signaling pathways. Owing to our results, AF is associated with an upregulation of AT1 in the left atrium, but not in the right atrium. This suggests a pathophysiological role of AT1 in AF (3,6,7).
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References
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1. Allessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardivasc Res. 2002;54:230–246[Abstract/Free Full Text]
2. Nakashima H, Kumagai K, Urata H, Gondo N, Ideishi M, Arakawa K. Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation. 2000;101:2612–2617[Abstract/Free Full Text]
3. Boldt A, Wetzel U, Weigl J, et al. Expression of angiotensin II receptors in human left and right atrial tissue in atrial fibrillation with and without underlying mitral valve disease. J Am Coll Cardiol. 2003;42:1785–1792[Abstract/Free Full Text]
4. Goette A, Arndt M, Röcken C, et al. Regulation of angiotensin II receptor subtypes during atrial fibrillation in humans. Circulation. 2000;101:2678–2681[Abstract/Free Full Text]
5. Allessie MA, Boyden PA, Camm AJ, et al. Pathophysiology and prevention of atrial fibrillation. Circulation. 2001;103:769–777[Free Full Text]
6. Kumagai K, Nakashima H, Urata H, Gondo N, Arakawa K, Saku K. Effects of angiotensin II type-1 receptor antagonist on electrical and structural remodeling in atrial fibrillation. J Am Coll Cardiol. 2003;41:2197–2204[Abstract/Free Full Text]
7. Madrid AH, Bueno MG, Rebollo JM, et al. Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Circulation. 2002;106:331–336[Abstract/Free Full Text]
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