Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure etiology and correlates to clinical variables

Am J Physiol Heart Circ Physiol. 2012 Aug 1;303(3):H368-76. doi: 10.1152/ajpheart.01061.2011. Epub 2012 Jun 8.


Downregulation of β(1)- adrenergic receptors (β(1)-ARs) and increased expression/function of G-protein-coupled receptor kinase 2 (GRK2) have been observed in human heart failure, but changes in expression of other ARs and GRKs have not been established. Another unresolved question is the incidence of these compensatory mechanisms depending on heart failure etiology and treatment. To analyze these questions, we quantified the mRNA/protein expressions of six ARs (α(1A), α(1B), α(1D), β(1), β(2), and β(3)) and three GRKs (GRK2, GRK3, and GRK5) in left (LV) and right ventricle (RV) from four donors, 10 patients with ischemic cardiomyopathy (IC), 14 patients with dilated cardiomyopathy (DC), and 10 patients with nonischemic, nondilated cardiopathies (NINDC). We correlated the changes in the expressions of ARs and GRKs with clinical variables such as left ventricular ejection fraction (LVEF) and left ventricular end-systolic and left ventricular end-diastolic diameter (LVESD and LVEDD, respectively). The main findings were 1) the expression of the α(1A)-AR in the LV positively correlates with LVEF; 2) the expression of GRK3 and GRK5 inversely correlates with LVESD and LVEDD, supporting previous observations about a protective role for both kinases in failing hearts; and 3) β(1)-AR expression is downregulated in the LV and RV of IC, in the LV of DC, and in the RV of NINDC. This difference, better than an increased expression of GRK2 (not observed in IC), determines the lower LVEF in IC and DC vs. NINDC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Cardiomyopathies / drug therapy
  • Cardiomyopathies / etiology*
  • Cardiomyopathies / genetics
  • Cardiomyopathies / metabolism*
  • Cardiomyopathies / physiopathology
  • Cardiomyopathy, Dilated / drug therapy
  • Cardiomyopathy, Dilated / etiology
  • Cardiomyopathy, Dilated / genetics
  • Cardiomyopathy, Dilated / metabolism
  • Cardiomyopathy, Dilated / physiopathology
  • Female
  • G-Protein-Coupled Receptor Kinases / genetics*
  • Genotype
  • Heart Failure / drug therapy
  • Heart Failure / etiology*
  • Heart Failure / genetics
  • Heart Failure / metabolism*
  • Heart Failure / physiopathology
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Myocardial Ischemia / complications*
  • Myocardial Ischemia / physiopathology
  • Myocardium / chemistry*
  • Phenotype
  • RNA, Messenger / analysis
  • Receptors, Adrenergic / analysis*
  • Receptors, Adrenergic / genetics
  • Spain
  • Stroke Volume
  • Ventricular Function, Left


  • RNA, Messenger
  • Receptors, Adrenergic
  • G-Protein-Coupled Receptor Kinases