Differential G protein receptor kinase 2 expression in compensated hypertrophy and heart failure after myocardial infarction in the rat.
The onset of heart failure is associated with characteristic changes in myocardial expression of G protein receptor kinase 2 (GRK2). Although, GRK2 significantly contributes to the regulation of myocardial function in the failing heart, the GRK2 expression during cardiac hypertrophy without heart failure remains to be explored. We here report a differential expression of GRK2 in cardiac hypertrophy with or without heart failure in response to a myocardial infarction in the rat. Postmyocardial infarction animals were divided into two groups depending on the absence or presence of pulmonary edema, which is a manifestation of heart failure. Remarkably, cardiac GRK2 expression and activity were inhibited in animals with cardiac hypertrophy without heart failure, whereas animals with heart failure had elevated GRK2. Thus, three weeks after the infarction cardiac GRK2 expression in animals with hypertrophy alone was decreased to 0.34 of control, whereas in the group of animals with heart failure GRK2 expression was 1.89-fold higher than in sham-operated animals. GRK2 activity was affected in a similar way, three and nine weeks after the infarction cardiac GRK2 activity was reduced to 0.58 and 0.62 in animals with hypertrophy without heart failure when compared to sham operated animals. By contrast, GRK2 activity was increased by 1.32- and 1.21-fold three and nine weeks postinfarction in animals with heart failure when compared to sham animals. These data suggest that GRK2 expression is differentially regulated in hypertrophic, non-failing and hypertrophic, failing hearts.
Theilade
J
J
Laboratory for Molecular Cardiology, 20, Juliane Mariesvej, 2100 Copenhagen, Denmark.
Strøm
C
C
Christiansen
T
T
Haunsø
S
S
Sheikh
S P
SP
D000818:Animals; D015153:Blotting, Western; D006332:Cardiomegaly / Q000201:enzymology* / Q000209:etiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis*; D004195:Disease Models, Animal; D054769:G-Protein-Coupled Receptor Kinase 2; D006333:Heart Failure / Q000201:enzymology* / Q000209:etiology; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000201:enzymology*; D051381:Rats; D013997:Time Factors; D051552:beta-Adrenergic Receptor Kinases
D017868:Cyclic AMP-Dependent Protein Kinases; C496569:Grk2 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2