title: Induction of myocardial insulin-like growth factor-I gene expression in left ventricular hypertrophy.
abstract: BACKGROUND
  Left ventricular hypertrophy is a generalized adaptation to increased afterload, but the growth factors mediating this response have not been identified. To explore whether the hypertrophic response was associated with changes in local insulin-like growth factor-I (IGF-I) gene regulation, we examined the induction of the cardiac IGF-I gene in three models of systolic hypertension and resultant hypertrophy.
  
  
  RESULTS
  The model systems were suprarenal aortic constriction, uninephrectomized spontaneously hypertensive rats (SHR), and uninephrectomized, deoxycorticosterone-treated, saline-fed rats (DOCA salt). Systolic blood pressure reached hypertensive levels at 3 to 4 weeks in all three systems. A differential increase in ventricular weight to body weight (hypertrophy) occurred at 3 weeks in the SHR and aortic constriction models and at 4 weeks in the DOCA salt model. Ventricular IGF-I mRNA was detected by solution hybridization/RNase protection assay. IGF-I mRNA levels increased in all three systems coincident with the onset of hypertension and the development of ventricular hypertrophy. Maximum induction was 10-fold over control at 5 weeks in the aortic constriction model, 8-fold at 3 weeks in the SHR, and 6-fold at 6 weeks in the DOCA salt model. IGF-I mRNA levels returned to control values by the end of the experimental period despite continued hypertension and hypertrophy in all three systems. In contrast, ventricular c-myc mRNA content increased twofold to threefold at 1 week and returned to control levels by 2 weeks. Ventricular IGF-I receptor mRNA levels were unchanged over the time course studied. The increased ventricular IGF-I mRNA content was reflected in an increased ventricular IGF-I protein content, as determined both by radioimmunoassay and immunofluorescence histochemistry.
  
  
  CONCLUSIONS
  We conclude that (1) hypertension induces significant increases in cardiac IGF-I mRNA and protein that occur coordinately with its onset and early in the development of hypertrophy, (2) IGF-I mRNA levels normalize as the hypertrophic response is established, (3) in comparison to IGF-I, both c-myc and IGF-I receptor genes are differentially controlled in experimental hypertension. These findings suggest that IGF-I may participate in initiating ventricular hypertrophy in response to altered loading conditions. The consistency of these findings in models of high-, moderate-, and low-renin hypertension suggests that they occur independently of the systemic renin-angiotensin endocrine axis.
authors.affiliation: Department of Medicine, New York University Medical Center, NY 10016.
authors.forename: T J
authors.initials: TJ
authors.lastname: Donohue
authors.forename: L D
authors.initials: LD
authors.lastname: Dworkin
authors.forename: M N
authors.initials: MN
authors.lastname: Lango
authors.forename: K
authors.initials: K
authors.lastname: Fliegner
authors.forename: R P
authors.initials: RP
authors.lastname: Lango
authors.forename: J A
authors.initials: JA
authors.lastname: Benstein
authors.forename: W R
authors.initials: WR
authors.lastname: Slater
authors.forename: V M
authors.initials: VM
authors.lastname: Catanese
mesh_terms: D000818:Animals; D001011:Aorta; D003900:Desoxycorticosterone; D015870:Gene Expression; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000209:etiology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008026:Ligation; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009392:Nephrectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D017451:Receptors, Somatomedin / Q000235:genetics; D012965:Sodium Chloride
chemical_list: D012333:RNA, Messenger; D017451:Receptors, Somatomedin; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D007334:Insulin-Like Growth Factor I