Aims To elucidate the cellular mechanisms of cardioprotection of b-blockers in patients with heart failure, we investigated the effects of b-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 b-blocker in 17 DCM patients. The messenger ribonucleic acid expression of collagen Types I and III (Col I and III) and transforming growth factor-b 1 (TGF-b 1 ) of right

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... lar 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 123 I-metaiodobenzylguanidine from the heart. Left ventricular ejection fraction (21+7 vs. 35 + 9%) and WR (53 + 14 vs. 42 + 13%) improved significantly. Before the b-blocker treatment, the expressions of both Col I (r ¼ 0.560, P ¼ 0.041) and Col III (r ¼ 0.630, P ¼ 0.008) genes were correlated with WR. The expression levels of both Col I (1.08 + 0.72 vs. 0.65 + 0.26, P ¼ 0.024) and Col III (2.06 + 1.81 vs. 1.05 + 0.74, P ¼ 0.018) were reduced by a b-blocker. Changes in TGF-b 1 correlated with those in WR (r ¼ 0.606, P ¼ 0.002). Conclusion b-Blockers are considered to inhibit the expression of collagen-related genes in DCM, which seems to be mediated by TGF-b 1 .