Reduced beta 1 receptor messenger RNA abundance in the failing human heart

J Clin Invest. 1993 Dec;92(6):2737-45. doi: 10.1172/JCI116891.


Heart failure in humans is characterized by alterations in myocardial adrenergic signal transduction, the most prominent of which is down-regulation of beta 1-adrenergic receptors. We tested the hypothesis that down-regulation of beta 1-adrenergic receptors in the failing human heart is related to decreased steady-state levels of beta 1 receptor mRNA. Due to the extremely low abundance of beta 1 receptor mRNA, measurements were possible only by quantitative polymerase chain reaction (QPCR) or by RNase protection methods. Because the beta 1 receptor gene is intronless and beta 1 receptor mRNA abundance is low, QPCR yielded genomic amplification in total RNA, and mRNA measurements had to be performed in poly (A)(+)-enriched RNA. By QPCR the concentration of beta 1 receptor mRNA varied from 0.34 to 7.8 x 10(7) molecules/microgram poly(A)(+)-enriched RNA, and the assay was sensitive to 16.7 zeptomol. Using 100-mg aliquots of left ventricular myocardium obtained from organ donors (nonfailing ventricles, n = 12) or heart transplant recipients (failing ventricles, n = 13), the respective beta 1 mRNA levels measured by QPCR were 4.2 +/- 0.7 x 10(7)/micrograms vs. 2.10 +/- 0.3 x 10(7)/micrograms (P = 0.006). In these same nonfailing and failing left ventricles the respective beta 1-adrenergic receptor densities were 67.9 +/- 6.9 fmol/mg vs. 29.6 +/- 3.5 fmol/mg (P = 0.0001). Decreased mRNA abundance in the failing ventricles was confirmed by RNase protection assays in total RNA, which also demonstrated a 50% reduction in beta 1 message abundance. We conclude that down-regulation of beta 1 receptor mRNA contributes to down-regulation of beta 1 adrenergic receptors in the failing human heart.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antisense Elements (Genetics)
  • Base Sequence
  • DNA / isolation & purification
  • DNA / metabolism
  • DNA Primers
  • Heart Failure / metabolism*
  • Heart Failure / surgery
  • Heart Transplantation
  • Heart-Lung Transplantation
  • Humans
  • Molecular Sequence Data
  • Myocardium / metabolism*
  • Polymerase Chain Reaction / methods
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / isolation & purification
  • RNA, Messenger / metabolism*
  • Receptors, Adrenergic, beta-1 / biosynthesis*
  • Receptors, Adrenergic, beta-2 / biosynthesis
  • Reference Values


  • Antisense Elements (Genetics)
  • DNA Primers
  • RNA, Messenger
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • DNA