Advertisement

Research Article Free access | 10.1172/JCI119770

Changes in gene expression in the intact human heart. Downregulation of alpha-myosin heavy chain in hypertrophied, failing ventricular myocardium.

B D Lowes, W Minobe, W T Abraham, M N Rizeq, T J Bohlmeyer, R A Quaife, R L Roden, D L Dutcher, A D Robertson, N F Voelkel, D B Badesch, B M Groves, E M Gilbert, and M R Bristow

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Lowes, B. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Minobe, W. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Abraham, W. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Rizeq, M. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Bohlmeyer, T. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Quaife, R. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Roden, R. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Dutcher, D. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Robertson, A. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Voelkel, N. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Badesch, D. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Groves, B. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Gilbert, E. in: JCI | PubMed | Google Scholar

Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262, USA.

Find articles by Bristow, M. in: JCI | PubMed | Google Scholar

Published November 1, 1997 - More info

Published in Volume 100, Issue 9 on November 1, 1997
J Clin Invest. 1997;100(9):2315–2324. https://doi.org/10.1172/JCI119770.
© 1997 The American Society for Clinical Investigation
Published November 1, 1997 - Version history
View PDF
Abstract

Using quantitative RT-PCR in RNA from right ventricular (RV) endomyocardial biopsies from intact nonfailing hearts, and subjects with moderate RV failure from primary pulmonary hypertension (PPH) or idiopathic dilated cardiomyopathy (IDC), we measured expression of genes involved in regulation of contractility or hypertrophy. Gene expression was also assessed in LV (left ventricular) and RV free wall and RV endomyocardium of hearts from end-stage IDC subjects undergoing heart transplantation or from nonfailing donors. In intact failing hearts, downregulation of beta1-receptor mRNA and protein, upregulation of atrial natriuretic peptide mRNA expression, and increased myocyte diameter indicated similar degrees of failure and hypertrophy in the IDC and PPH phenotypes. The only molecular phenotypic difference between PPH and IDC RVs was upregulation of beta2-receptor gene expression in PPH but not IDC. The major new findings were that (a) both nonfailing intact and explanted human ventricular myocardium expressed substantial amounts of alpha-myosin heavy chain mRNA (alpha-MHC, 23-34% of total), and (b) in heart failure alpha-MHC was downregulated (by 67-84%) and beta-MHC gene expression was upregulated. We conclude that at the mRNA level nonfailing human heart expresses substantial alpha-MHC. In myocardial failure this alteration in gene expression of MHC isoforms, if translated into protein expression, would decrease myosin ATPase enzyme velocity and slow speed of contraction.

Version history
  • Version 1 (November 1, 1997): No description
Advertisement
Advertisement