Inhibition of matrix metalloproteinases prevents cardiac hypertrophy induced by beta-adrenergic stimulation in rats.
Insulin-like growth factor (IGF) -I is one of the candidates for cardiac hypertrophy induced by beta-adrenergic stimulation. However, the mechanisms by which the biologic actions of IGF-I are regulated under this condition remain unclear. IGF-I becomes bioavailable for its receptors upon its dissociation from IGF-binding protein (IGFBP) through IGFBP degradation. Because matrix metalloproteinases (MMPs) have been implicated in the degradation of IGFBPs, the authors investigated the role of MMPs in the regulation of the IGF-I action through the degradation of IGFBPs in cardiac hypertrophy induced by beta-adrenergic stimulation. They examined the expression of MMPs in cardiac tissues of rats infused with isoproterenol (3 mg/kg per day), the effect of a MMP inhibitor, SI-27 (5 mg/rat per day), on cardiac hypertrophy, and the expression of IGF-I and IGFBP-3. MMP-1 and -2 activities increased and IGFBP-3 was degraded in heart hypertrophied by isoproterenol. MMP inhibition caused a regression in the myocyte hypertrophy in association with the suppression of both IGF-I protein in myocytes and the degradation of IGFBP-3 protein. These results suggest that the induction of myocyte hypertrophy by isoproterenol is mediated, at least in part, by a modulation of the IGF-I axis.
Miura
Shoko
S
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machio, Aoba-ku, Sendai 980-8574, Japan.
Ohno
Isao
I
Suzuki
Jun
J
Suzuki
Ko
K
Okada
Shinji
S
Okuyama
Akira
A
Nawata
Jun
J
Ikeda
Jun
J
Shirato
Kunio
K
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000633:toxicity; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D061965:Matrix Metalloproteinase Inhibitors; D007334:Insulin-Like Growth Factor I; D007545:Isoproterenol