Changes in myocardial gene expression associated with β-blocker therapy in patients with chronic heart failure

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 Ca2+ 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+-Ca2+ 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 Ca2+ handlings in the failing heart.