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European Heart Journal Advance Access published online on October 4, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi492
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European Heart Journal © The European Society of Cardiology 2005; all rights reserved
Received January 3, 2005
Revised August 10, 2005
Accepted August 18, 2005

Clinical research

Increased gene expression of collagen Types I and III is inhibited by {beta}-receptor blockade in patients with dilated cardiomyopathy

Junsho Shigeyama 1, Yoshio Yasumura 1, Aiji Sakamoto 2, Yoshio Ishida 3, Tatsuya Fukutomi 4, Makoto Itoh 4, Kunio Miyatake 1, and Masafumi Kitakaze 1*

1 Division of Cardiology, Department of Medicine, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
2 Division of Biotechnology, National Cardiovascular Center Research Institute, Osaka, Japan
3 Division of Radiology, National Cardiovascular Center, Osaka, Japan
4 Department of Internal Medicine and Bioregulation, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan

* To whom correspondence should be addressed.
Masafumi Kitakaze, E-mail: kitakaze{at}hsp.ncvc.go.jp


  Abstract

Aims To elucidate the cellular mechanisms of cardioprotection of {beta}-blockers in patients with heart failure, we investigated the effects of {beta}-blockers on collagen synthesis in patients with dilated cardiomyopathy (DCM).

Methods and results We examined the gene expression before and 4 months after the administration of a {beta}-blocker in 17 DCM patients. The messenger ribonucleic acid expression of collagen Types I and III (Col I and III) and transforming growth factor-{beta}1 (TGF-{beta}1) of right ventricular tissues obtained by the endomyocardial biopsy were assessed by quantitative reverse transcriptase-polymerase chain reaction. Cardiac sympathetic nerve activity was assessed by the washout rate (WR) of 123I-metaiodobenzylguanidine from the heart. Left ventricular ejection fraction (21 ± 7 vs. 35 ± 9%) and WR (53 ± 14 vs. 42 ± 13%) improved significantly. Before the {beta}-blocker treatment, the expressions of both Col I (r = 0.560, P = 0.041) and Col III (r = 0.630, P = 0.008) genes were correlated with WR. The expression levels of both Col I (1.08 ± 0.72 vs. 0.65 ± 0.26, P = 0.024) and Col III (2.06 ± 1.81 vs. 1.05 ± 0.74, P = 0.018) were reduced by a {beta}-blocker. Changes in TGF-{beta}1 correlated with those in WR (r = 0.606, P = 0.002).

Conclusion {beta}-Blockers are considered to inhibit the expression of collagen-related genes in DCM, which seems to be mediated by TGF-{beta}1.

Keywords: Collagen synthesis; {beta}-Blocker; Myocardial gene expression; Heart failure; Dilated cardiomyopathy.
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