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

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 o f the GRK-arrestin system, has not been studied in myocardial tissue. Thus myocardial expression and cellular distribution of the different GRK and ar restin 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 -arr estin-1, and beta -arrestin-2 mRNA levels, but not that of GRK3, were induc ed in the failing hearts. Consistently, Western blot analysis of tissue ext racts 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-op erated rats (P < 0.05). Immunohistochemical analysis of myocardial tissue s ections and Western blot analysis of isolated cells revealed localization o f 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 c onclusion, myocardial mRNA and protein levels of GRK2, GRK5, and beta -arre stin-1 are induced in postinfarction failure in rats. The immunohistochemic al analysis suggests that GRK2 and beta -arrestin-1 may act as primary regu lators of endothelial function. Conversely, the cellular distribution of GR K3 and GRK5 implicates these isoforms as putative regulators of cardiac myo cyte function.