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Induction of cardiac insulin-like growth factor I gene expression in pressure overload hypertrophy
M C Hanson1, K A Fath, R W Alexander
1Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322.
Abstract:
Molecular mechanisms regulating the cardiac hypertrophic response to increased hemodynamic load are understood poorly. Insulin-like growth factor I (IGF I) is a mitogen that is thought to play a key role in pre- and postnatal growth. To investigate a possible role of IGF I in the cardiac response to pressure overload, rats underwent banding of the ascending aorta immediately above the aortic valve using a hemoclip, or a sham procedure. An analysis of left-ventricular RNA by Northern hybridization using a 32P-labeled IGF I cDNA revealed four messenger ribonucleic acid transcripts of 7.6, 4.6, 1.7, and 0.9 to 1.2 Kb. Insulin-like growth factor I messenger ribonucleic acid was quantitated by ribonuclease protection assays using a rat exon 3 riboprobe. There was a sustained increase in IGF I mRNA levels that correlated temporally with the development of left ventricular hypertrophy. These results indicate that left ventricular pressure overload is associated with an induction of cardiac IGF I gene expression. Insulin-like growth factor I may play a role in the response to increases in wall stress and likely contribute to cardiac hypertrophy.