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.Methods and 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

Basal and IGF-I-dependent regulation of potassium channels by MAP kinases and PI3-kinase during eccentric cardiac hypertrophy

“…Addition of IGF-I to cultured newborn rat cardiocytes stimulates the expression of muscle-specific genes that induce myocyte hypertrophy (28). In addition, there is sufficient evidence showing that IGF-I mRNA and protein increase in parallel with the development of cardiac hypertrophy (9). Furthermore, in the volume-overload model we have shown that cardiac myofibers have an increased receptor affinity to IGF-I, which corroborated with the induction of eccentric hypertrophy (20).…”

Insulin-like Growth Factor-I Rapidly Activates Multiple Signal Transduction Pathways in Cultured Rat Cardiac Myocytes

“…In cultured neonatal cardiac myocytes, IGF-I induces an early and sustained expression of the muscle-specific genes for troponin I and myosin light chain-2 with myocyte size almost doubling after 48 h of treatment with IGF-I (14). An increase in left ventricular IGF-I mRNA and its protein has been described in pressure overload cardiac hypertrophy in various models of hypertension; this suggests that IGF-I may be an important mediator of an adaptive hypertrophic response (21,45,46). However, the results of overexpression of IGF-I in transgenic mice have been contradictory (22,47).…”

“…Increased plasma IGF-I concentrations have been reported in patients with hypertension and cardiac hypertrophy (20). The hypertension induces significant increases in cardiac IGF-I mRNA and protein in parallel with the onset and early development of experimental cardiac hypertrophy; this is followed by a normalization of the IGF-I mRNA once the hypertrophic response is established (21). A very recent report has established that the overexpression of IGF-I in cardiac myocytes leads to cardiomegaly mediated by an increased number of cells in the heart (22).…”

ACE inhibition in aortic stenosis: dangerous medicine or golden opportunity?

“…22 Changes of this nature, such as increased expression of the beta-myosin heavy chain mRNA and insulin-like growth factor production, are similar to those seen in human cardiomyocytes with pressure overload induced hypertrophy in vivo. 23,24 The pathological remodelling of the ventricle occurring in pressure overload is not however simply caused by increases in myocyte size, but also involves a progressive interstitial fibrosis. Angiotensin II binding to the AT 1 receptor has also been shown to be responsible for a significant increase in collagen synthesis by cardiac fibroblasts.…”