In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 281, No. 6 ( 2001-12-01), p. H2490-H2499
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, β-arrestin-1, and β-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 β-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 β-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 β-arrestin-1 are induced in postinfarction failure in rats. The immunohistochemical analysis suggests that GRK2 and β-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.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.2001.281.6.H2490
Language:
English
Publisher:
American Physiological Society
Publication Date:
2001
detail.hit.zdb_id:
1477308-9
SSG:
12
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