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European Heart Journal Advance Access originally published online on October 4, 2005
European Heart Journal 2005 26(24):2698-2705; doi:10.1093/eurheartj/ehi492
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© The European Society of Cardiology 2005. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

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

Junsho Shigeyama1, Yoshio Yasumura1, Aiji Sakamoto2, Yoshio Ishida3, Tatsuya Fukutomi4, Makoto Itoh4, Kunio Miyatake1 and Masafumi Kitakaze1,*

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

Received 3 January 2005; revised 10 August 2005; accepted 18 August 2005; online publish-ahead-of-print 4 October 2005.

* Corresponding author. Tel: +81 6 6833 5012; fax: +81 6 6872 7486. E-mail address: kitakaze{at}hsp.ncvc.go.jp

Aims To elucidate the cellular mechanisms of cardioprotection of ß-blockers in patients with heart failure, we investigated the effects of ß-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 ß-blocker in 17 DCM patients. The messenger ribonucleic acid expression of collagen Types I and III (Col I and III) and transforming growth factor-ß1 (TGF-ß1) 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 ß-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 ß-blocker. Changes in TGF-ß1 correlated with those in WR (r=0.606, P=0.002).

Conclusion ß-Blockers are considered to inhibit the expression of collagen-related genes in DCM, which seems to be mediated by TGF-ß1.

Key Words: Collagen synthesis • ß-Blocker • Myocardial gene expression • Heart failure • Dilated cardiomyopathy


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