Myocardial distribution and regulation of GRK and beta -arrestin isoforms in congestive heart failure in rats

• Published in: American journal of physiology. Heart and circulatory physiology 2001-12, Vol.281 (6), p.H2490-H2499
• Main Authors: Vinge, Leif Erik, Oie, Erik, Andersson, Yvonne, Grogaard, Haakon K, Andersen, Geir O, Attramadal, Havard
• Format: Article
• Language: English
• Subjects: Animals; Arrestins - analysis; Arrestins - genetics; Arrestins - metabolism; Atrial Natriuretic Factor - genetics; beta-Adrenergic Receptor Kinases; beta-Arrestin 1; beta-Arrestin 2; beta-Arrestins; Blotting, Western; COS Cells; Cyclic AMP-Dependent Protein Kinases - analysis; Cyclic AMP-Dependent Protein Kinases - genetics; Cyclic AMP-Dependent Protein Kinases - metabolism; Fibroblasts - cytology; Fibroblasts - enzymology; G-Protein-Coupled Receptor Kinase 2; G-Protein-Coupled Receptor Kinase 3; G-Protein-Coupled Receptor Kinase 5; Gene Expression Regulation, Enzymologic; Heart Failure - metabolism; Immunohistochemistry; Male; Myocardium - chemistry; Myocardium - cytology; Myocardium - enzymology; Protein-Serine-Threonine Kinases - analysis; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Rats; Rats, Wistar; RNA, Messenger - analysis; Transfection; Ventricular Pressure - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.2001.281.6.H2490

1  Institute for Surgical Research, 2  MerckSharp & Dohme Cardiovascular Research Center, and 3  Department of Pharmacology, Rikshospitalet University Hospital, University of Oslo, N-0027 Oslo, Norway 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, -arrestin-1, and -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 -arrestin-1, respectively, 7 days after induction of myocardial infarction compared with the sham-operated rats ( P