Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents

Brian D. Lowes, Edward M. Gilbert, William T. Abraham, Wayne A. Minobe, Patti Larrabee, Debra Ferguson, Eugene E. Wolfel, Jo Ann Lindenfeld, Tatiana Tsvetkova, Alastair D. Robertson, Robert A. Quaife, Michael R. Bristow

Research output: Contribution to journalArticle

391 Citations (Scopus)

Abstract

Background: Beta-blocker therapy may improve cardiac function in patients with idiopathic dilated cardiomyopathy. We tested the hypothesis that betablocker therapy produces favorable functional effects in dilated cardiomyopathy by altering the expression of myocardial genes that regulate contractility and pathologic hypertrophy. Methods: We randomly assigned 53 patients with idiopathic dilated cardiomyopathy to treatment with a β-adrenergic-receptor blocking agent (metoprolol or carvedilol) or placebo. The amount of messenger RNA (mRNA) for contractility-regulating genes (those encoding β 1- and β 2-adrenergic receptors, calcium ATPase in the sarcoplasmic reticulum, and α- and β-myosin heavy-chain isoforms) and of genes associated with pathologic hypertrophy (β-myosin heavy chain and atrial natriuretic peptide) was measured with a quantitative reverse-transcription polymerase chain reaction in total RNA extracted from biopsy specimens of the right ventricular septal endomyocardium. Myocardial levels of β-adrenergic receptors were also measured. Measurements were conducted at base line and after six months of treatment, and changes in gene expression were compared with changes in the left ventricular ejection fraction as measured by radionuclide ventriculography. Results: Twenty-six of 32 beta-blocker-treated patients (those with complete mRNA measurements) had an improvement in left ventricular ejection fraction of at least 5 ejection-fraction (EF) units (mean [±SE] increase, 18.8±1.8). As compared with the six betablocker-treated patients who did not have a response (mean change, a decrease of 2.5±1.8 EF units), those who did have a response had an increase in sarcoplasmic-reticulum calcium ATPase mRNA and α-myosin heavy chain mRNA and a decrease in β-myosin heavy chain mRNA. The change in sarcoplasmic-reticulum calcium ATPase was not present in the patients in the placebo group who had a spontaneous response. There were no differences between those who had a response and those who did not in terms of the change in mRNA or protein expression of β-adrenergic receptors. Conclusions: In idiopathic dilated cardiomyopathy, functional improvement related to treatment with beta-blockers is associated with changes in myocardial gene expression.

Original languageEnglish (US)
Pages (from-to)1357-1365
Number of pages9
JournalNew England Journal of Medicine
Volume346
Issue number18
DOIs
StatePublished - May 2 2002

Fingerprint

Dilated Cardiomyopathy
Myosin Heavy Chains
Sarcoplasmic Reticulum Calcium-Transporting ATPases
Gene Expression
Adrenergic Receptors
Messenger RNA
Stroke Volume
Hypertrophy
Placebos
Radionuclide Ventriculography
Therapeutics
Metoprolol
Adrenergic Antagonists
Atrial Natriuretic Factor
Genes
Reverse Transcription
Protein Isoforms
RNA
Biopsy
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lowes, B. D., Gilbert, E. M., Abraham, W. T., Minobe, W. A., Larrabee, P., Ferguson, D., ... Bristow, M. R. (2002). Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents. New England Journal of Medicine, 346(18), 1357-1365. https://doi.org/10.1056/NEJMoa012630

Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents. / Lowes, Brian D.; Gilbert, Edward M.; Abraham, William T.; Minobe, Wayne A.; Larrabee, Patti; Ferguson, Debra; Wolfel, Eugene E.; Lindenfeld, Jo Ann; Tsvetkova, Tatiana; Robertson, Alastair D.; Quaife, Robert A.; Bristow, Michael R.

In: New England Journal of Medicine, Vol. 346, No. 18, 02.05.2002, p. 1357-1365.

Research output: Contribution to journalArticle

Lowes, BD, Gilbert, EM, Abraham, WT, Minobe, WA, Larrabee, P, Ferguson, D, Wolfel, EE, Lindenfeld, JA, Tsvetkova, T, Robertson, AD, Quaife, RA & Bristow, MR 2002, 'Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents', New England Journal of Medicine, vol. 346, no. 18, pp. 1357-1365. https://doi.org/10.1056/NEJMoa012630
Lowes, Brian D. ; Gilbert, Edward M. ; Abraham, William T. ; Minobe, Wayne A. ; Larrabee, Patti ; Ferguson, Debra ; Wolfel, Eugene E. ; Lindenfeld, Jo Ann ; Tsvetkova, Tatiana ; Robertson, Alastair D. ; Quaife, Robert A. ; Bristow, Michael R. / Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents. In: New England Journal of Medicine. 2002 ; Vol. 346, No. 18. pp. 1357-1365.
@article{c1afff85096f438f8ca43abc93756558,
title = "Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents",
abstract = "Background: Beta-blocker therapy may improve cardiac function in patients with idiopathic dilated cardiomyopathy. We tested the hypothesis that betablocker therapy produces favorable functional effects in dilated cardiomyopathy by altering the expression of myocardial genes that regulate contractility and pathologic hypertrophy. Methods: We randomly assigned 53 patients with idiopathic dilated cardiomyopathy to treatment with a β-adrenergic-receptor blocking agent (metoprolol or carvedilol) or placebo. The amount of messenger RNA (mRNA) for contractility-regulating genes (those encoding β 1- and β 2-adrenergic receptors, calcium ATPase in the sarcoplasmic reticulum, and α- and β-myosin heavy-chain isoforms) and of genes associated with pathologic hypertrophy (β-myosin heavy chain and atrial natriuretic peptide) was measured with a quantitative reverse-transcription polymerase chain reaction in total RNA extracted from biopsy specimens of the right ventricular septal endomyocardium. Myocardial levels of β-adrenergic receptors were also measured. Measurements were conducted at base line and after six months of treatment, and changes in gene expression were compared with changes in the left ventricular ejection fraction as measured by radionuclide ventriculography. Results: Twenty-six of 32 beta-blocker-treated patients (those with complete mRNA measurements) had an improvement in left ventricular ejection fraction of at least 5 ejection-fraction (EF) units (mean [±SE] increase, 18.8±1.8). As compared with the six betablocker-treated patients who did not have a response (mean change, a decrease of 2.5±1.8 EF units), those who did have a response had an increase in sarcoplasmic-reticulum calcium ATPase mRNA and α-myosin heavy chain mRNA and a decrease in β-myosin heavy chain mRNA. The change in sarcoplasmic-reticulum calcium ATPase was not present in the patients in the placebo group who had a spontaneous response. There were no differences between those who had a response and those who did not in terms of the change in mRNA or protein expression of β-adrenergic receptors. Conclusions: In idiopathic dilated cardiomyopathy, functional improvement related to treatment with beta-blockers is associated with changes in myocardial gene expression.",
author = "Lowes, {Brian D.} and Gilbert, {Edward M.} and Abraham, {William T.} and Minobe, {Wayne A.} and Patti Larrabee and Debra Ferguson and Wolfel, {Eugene E.} and Lindenfeld, {Jo Ann} and Tatiana Tsvetkova and Robertson, {Alastair D.} and Quaife, {Robert A.} and Bristow, {Michael R.}",
year = "2002",
month = "5",
day = "2",
doi = "10.1056/NEJMoa012630",
language = "English (US)",
volume = "346",
pages = "1357--1365",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "18",

}

TY - JOUR

T1 - Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents

AU - Lowes, Brian D.

AU - Gilbert, Edward M.

AU - Abraham, William T.

AU - Minobe, Wayne A.

AU - Larrabee, Patti

AU - Ferguson, Debra

AU - Wolfel, Eugene E.

AU - Lindenfeld, Jo Ann

AU - Tsvetkova, Tatiana

AU - Robertson, Alastair D.

AU - Quaife, Robert A.

AU - Bristow, Michael R.

PY - 2002/5/2

Y1 - 2002/5/2

N2 - Background: Beta-blocker therapy may improve cardiac function in patients with idiopathic dilated cardiomyopathy. We tested the hypothesis that betablocker therapy produces favorable functional effects in dilated cardiomyopathy by altering the expression of myocardial genes that regulate contractility and pathologic hypertrophy. Methods: We randomly assigned 53 patients with idiopathic dilated cardiomyopathy to treatment with a β-adrenergic-receptor blocking agent (metoprolol or carvedilol) or placebo. The amount of messenger RNA (mRNA) for contractility-regulating genes (those encoding β 1- and β 2-adrenergic receptors, calcium ATPase in the sarcoplasmic reticulum, and α- and β-myosin heavy-chain isoforms) and of genes associated with pathologic hypertrophy (β-myosin heavy chain and atrial natriuretic peptide) was measured with a quantitative reverse-transcription polymerase chain reaction in total RNA extracted from biopsy specimens of the right ventricular septal endomyocardium. Myocardial levels of β-adrenergic receptors were also measured. Measurements were conducted at base line and after six months of treatment, and changes in gene expression were compared with changes in the left ventricular ejection fraction as measured by radionuclide ventriculography. Results: Twenty-six of 32 beta-blocker-treated patients (those with complete mRNA measurements) had an improvement in left ventricular ejection fraction of at least 5 ejection-fraction (EF) units (mean [±SE] increase, 18.8±1.8). As compared with the six betablocker-treated patients who did not have a response (mean change, a decrease of 2.5±1.8 EF units), those who did have a response had an increase in sarcoplasmic-reticulum calcium ATPase mRNA and α-myosin heavy chain mRNA and a decrease in β-myosin heavy chain mRNA. The change in sarcoplasmic-reticulum calcium ATPase was not present in the patients in the placebo group who had a spontaneous response. There were no differences between those who had a response and those who did not in terms of the change in mRNA or protein expression of β-adrenergic receptors. Conclusions: In idiopathic dilated cardiomyopathy, functional improvement related to treatment with beta-blockers is associated with changes in myocardial gene expression.

AB - Background: Beta-blocker therapy may improve cardiac function in patients with idiopathic dilated cardiomyopathy. We tested the hypothesis that betablocker therapy produces favorable functional effects in dilated cardiomyopathy by altering the expression of myocardial genes that regulate contractility and pathologic hypertrophy. Methods: We randomly assigned 53 patients with idiopathic dilated cardiomyopathy to treatment with a β-adrenergic-receptor blocking agent (metoprolol or carvedilol) or placebo. The amount of messenger RNA (mRNA) for contractility-regulating genes (those encoding β 1- and β 2-adrenergic receptors, calcium ATPase in the sarcoplasmic reticulum, and α- and β-myosin heavy-chain isoforms) and of genes associated with pathologic hypertrophy (β-myosin heavy chain and atrial natriuretic peptide) was measured with a quantitative reverse-transcription polymerase chain reaction in total RNA extracted from biopsy specimens of the right ventricular septal endomyocardium. Myocardial levels of β-adrenergic receptors were also measured. Measurements were conducted at base line and after six months of treatment, and changes in gene expression were compared with changes in the left ventricular ejection fraction as measured by radionuclide ventriculography. Results: Twenty-six of 32 beta-blocker-treated patients (those with complete mRNA measurements) had an improvement in left ventricular ejection fraction of at least 5 ejection-fraction (EF) units (mean [±SE] increase, 18.8±1.8). As compared with the six betablocker-treated patients who did not have a response (mean change, a decrease of 2.5±1.8 EF units), those who did have a response had an increase in sarcoplasmic-reticulum calcium ATPase mRNA and α-myosin heavy chain mRNA and a decrease in β-myosin heavy chain mRNA. The change in sarcoplasmic-reticulum calcium ATPase was not present in the patients in the placebo group who had a spontaneous response. There were no differences between those who had a response and those who did not in terms of the change in mRNA or protein expression of β-adrenergic receptors. Conclusions: In idiopathic dilated cardiomyopathy, functional improvement related to treatment with beta-blockers is associated with changes in myocardial gene expression.

UR - http://www.scopus.com/inward/record.url?scp=0037007679&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037007679&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa012630

DO - 10.1056/NEJMoa012630

M3 - Article

C2 - 11986409

AN - SCOPUS:0037007679

VL - 346

SP - 1357

EP - 1365

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 18

ER -