BACKGROUND: The left ventricular functional recovery by beta-blocker therapy is now attributed to time-dependent biologic effects on cardiomyocytes. METHODS AND RESULTS: To elucidate the cellular mechanism of these biologic effects, we treated 9 patients with dilated cardiomyopathy for 4 months with beta-blockers and examined the gene expressions linked to an improvement of left ventricular ejection fraction (EF). Gene expressions of the biopsied right ventricular endomyocardium were assessed by real-time reverse transcription-polymerase chain reaction. A decrease in beta-myosin heavy chain (1.23+/-0.49 versus 0.86+/-0.45, P<.05) was observed 4 months after the administration of beta-blockers. The expression levels of both sarcoplasmic reticulum Ca(2+) ATPase (SERCA) (0.80+/-0.28 versus 1.39+/-0.44, P<.01) and phospholamban (PLB) (0.49+/-0.08 versus 0.88+/-0.34, P<.05) increased, whereas the expression levels of Na(+)-Ca(2+) exchanger (NCX), beta-adrenoreceptor kinase 1, and ryanodine receptor 2 were unchanged. The SERCA/NCX ratio (0.68+/-0.14 versus 0.96+/-0.33, P<.05) also increased. The increase in SERCA mRNA expression correlated with the degree of changes in EF (%deltaEF) (r=0.679, P<.05), and none of changes in these genes expression correlated with changes in the plasma brain natriuretic peptide concentration. CONCLUSIONS: The functional recovery resulting from beta-blockers may be associated with the restoration of the unfavorable gene expression that controls Ca(2+) handlings in the failing heart.
BACKGROUND: The left ventricular functional recovery by beta-blocker therapy is now attributed to time-dependent biologic effects on cardiomyocytes. METHODS AND RESULTS: To elucidate the cellular mechanism of these biologic effects, we treated 9 patients with dilated cardiomyopathy for 4 months with beta-blockers and examined the gene expressions linked to an improvement of left ventricular ejection fraction (EF). Gene expressions of the biopsied right ventricular endomyocardium were assessed by real-time reverse transcription-polymerase chain reaction. A decrease in beta-myosin heavy chain (1.23+/-0.49 versus 0.86+/-0.45, P<.05) was observed 4 months after the administration of beta-blockers. The expression levels of both sarcoplasmic reticulum Ca(2+) ATPase (SERCA) (0.80+/-0.28 versus 1.39+/-0.44, P<.01) and phospholamban (PLB) (0.49+/-0.08 versus 0.88+/-0.34, P<.05) increased, whereas the expression levels of Na(+)-Ca(2+) exchanger (NCX), beta-adrenoreceptor kinase 1, and ryanodine receptor 2 were unchanged. The SERCA/NCX ratio (0.68+/-0.14 versus 0.96+/-0.33, P<.05) also increased. The increase in SERCA mRNA expression correlated with the degree of changes in EF (%deltaEF) (r=0.679, P<.05), and none of changes in these genes expression correlated with changes in the plasma brain natriuretic peptide concentration. CONCLUSIONS: The functional recovery resulting from beta-blockers may be associated with the restoration of the unfavorable gene expression that controls Ca(2+) handlings in the failing heart.
Authors: David P Kao; Brian D Lowes; Edward M Gilbert; Wayne Minobe; L Elaine Epperson; Leslie K Meyer; Debra A Ferguson; Ann Kirkpatrick Volkman; Ronald Zolty; C Douglas Borg; Robert A Quaife; Michael R Bristow Journal: Circ Cardiovasc Genet Date: 2015-01-30
Authors: Koichiro Kuwahara; Yanggan Wang; John McAnally; James A Richardson; Rhonda Bassel-Duby; Joseph A Hill; Eric N Olson Journal: J Clin Invest Date: 2006-11-09 Impact factor: 14.808
Authors: J A K Birkeland; I Sjaastad; T Brattelid; E Qvigstad; E R Moberg; K A Krobert; R Bjørnerheim; T Skomedal; O M Sejersted; J-B Osnes; F O Levy Journal: Br J Pharmacol Date: 2006-12-11 Impact factor: 8.739