title: Myocardial distribution and regulation of GRK and beta-arrestin isoforms in congestive heart failure in rats.
abstract: Myocardial G protein-coupled receptor kinase 2 (GRK2) has been shown to be involved in the pathophysiology of congestive heart failure (CHF). However, the cellular distribution of this isoform, as well as the other isoforms of the GRK-arrestin system, has not been studied in myocardial tissue. Thus myocardial expression and cellular distribution of the different GRK and arrestin isoforms were investigated in a rat model of CHF. Rats subjected to ligation of the left coronary artery or sham operation were euthanized 2, 7, or 42 days after the surgical procedure. Myocardial GRK2, GRK5, beta-arrestin-1, and beta-arrestin-2 mRNA levels, but not that of GRK3, were induced in the failing hearts. Consistently, Western blot analysis of tissue extracts from the nonischemic region of the left ventricle revealed 3.0-, 2.6-, and 1.5-fold elevations of GRK2, GRK5, and beta-arrestin-1, respectively, 7 days after induction of myocardial infarction compared with the sham-operated rats (P < 0.05). Immunohistochemical analysis of myocardial tissue sections and Western blot analysis of isolated cells revealed localization of GRK2 and beta-arrestin-1 predominantly in endothelial cells. Conversely, GRK3 was confined to cardiac myocytes. GRK5 immunostaining appeared to be homogeneously distributed in the cellular elements of the myocardium. In conclusion, myocardial mRNA and protein levels of GRK2, GRK5, and beta-arrestin-1 are induced in postinfarction failure in rats. The immunohistochemical analysis suggests that GRK2 and beta-arrestin-1 may act as primary regulators of endothelial function. Conversely, the cellular distribution of GRK3 and GRK5 implicates these isoforms as putative regulators of cardiac myocyte function.
authors.affiliation: Institute for Surgical Research, Rikshospitalet University Hospital, University of Oslo, N-0027 Oslo, Norway.
authors.forename: L E
authors.initials: LE
authors.lastname: Vinge
authors.forename: E
authors.initials: E
authors.lastname: Øie
authors.forename: Y
authors.initials: Y
authors.lastname: Andersson
authors.forename: H K
authors.initials: HK
authors.lastname: Grøgaard
authors.forename: G
authors.initials: G
authors.lastname: Andersen
authors.forename: H
authors.initials: H
authors.lastname: Attramadal
mesh_terms: D000818:Animals; D019390:Arrestins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000235:genetics; D015153:Blotting, Western; D019556:COS Cells; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D054769:G-Protein-Coupled Receptor Kinase 2; D054770:G-Protein-Coupled Receptor Kinase 3; D054774:G-Protein-Coupled Receptor Kinase 5; D015971:Gene Expression Regulation, Enzymologic; D006333:Heart Failure / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000166:cytology / Q000201:enzymology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D014162:Transfection; D017725:Ventricular Pressure / Q000502:physiology; D051552:beta-Adrenergic Receptor Kinases; D000071559:beta-Arrestin 1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
chemical_list: C000605256:Arrb1 protein, rat; C000605257:Arrb2 protein, rat; D019390:Arrestins; D012333:RNA, Messenger; D000071559:beta-Arrestin 1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D009320:Atrial Natriuretic Factor; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D054770:G-Protein-Coupled Receptor Kinase 3; C496569:Grk2 protein, rat; C517851:Grk3 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2; D054774:G-Protein-Coupled Receptor Kinase 5; C517897:Grk5 protein, rat