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


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 (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 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).


CONCLUSIONS
beta-Blockers are considered to inhibit the expression of collagen-related genes in DCM, which seems to be mediated by TGF-beta(1).
Shigeyama
Junsho
J
Division of Cardiology, Department of Medicine, National Cardiovascular Center, Osaka, Japan.
Yasumura
Yoshio
Y
Sakamoto
Aiji
A
Ishida
Yoshio
Y
Fukutomi
Tatsuya
T
Itoh
Makoto
M
Miyatake
Kunio
K
Kitakaze
Masafumi
M
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000319:Adrenergic beta-Antagonists; D024042:Collagen Type I; D024061:Collagen Type III; D018076:DNA, Complementary; D011506:Proteins; D012333:RNA, Messenger