Some Growth Factors Stimulate Cultured Adult Rabbit Ventricular Myocyte Hypertrophy in the Absence of Mechanical Loading

Abstract

Cultured adult rabbit cardiac myocytes treated with recombinant growth factors display enhanced rates of protein accumulation (ie, growth) in response to insulin and insulin-like growth factors (IGFs), but epidermal growth factor, acidic or basic fibroblast growth factor, and platelet-derived growth factor failed to increase contractile protein synthesis or growth of the heart cells. Insulin and IGF-1 increased growth rates by stimulating anabolic while simultaneously inhibiting catabolic pathways, whereas IGF-2 elevated growth modestly by apparently inhibiting lysosomal proteolysis. Neutralizing antibodies directed against either IGF-1 or IGF-2 or IGF binding protein 3 blocked protein accumulation. A monoclonal antibody directed against the IGF-1 receptor also inhibited changes in protein turnover provoked by recombinant human IGF-1 but not IGF-2. Of the other growth factors tested, only transforming growth factor-beta 1 increased the fractional rate of myosin heavy chain (MHC) synthesis, with beta-MHC synthesis being elevated and alpha-MHC synthesis being suppressed. However, the other growth factors were able to modestly stimulate the rate of DNA synthesis in this preparation. Bromodeoxyuridine labeling revealed that these growth factors increased DNA synthesis in myocytes and nonmyocytes alike, but the heart cells displayed neither karyokinesis or cytokinesis. In contrast, cocultures of cardiac myocytes and nonmyocytes and nonmyocyte-conditioned culture medium failed to enhance the rate of cardiac MHC synthesis or its accumulation, implying that quiescent heart cells do not respond to "conditioning" by cardiac nonmyocytes. These findings demonstrated that insulin and the IGFs promote passively loaded cultured adult rabbit heart cells to hypertrophy but suggest that other growth factors tested may be limited in this regard.

Soy diet worsens heart disease in mice

“…Since IGF-1 treatment of cardiac myocytes in culture increases β-MyHC synthesis (40,41), we explored the IGF-1/Akt/glycogen synthase kinase 3 (IGF-1/Akt/GSK3) cascade. Sex-dependent differences…”

Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer

“…2,3 The possibility of a direct action is supported by the data which show that VEGF receptors are present in rat cardiomyocytes, where VEGF has been shown to activate the mitogen-activated protein kinase cascade. 7,8 An effect of VEGF upon a population of circulating or resident cardiac stem cells, as recently proposed for the human heart, cannot be ruled out.…”

“…Growth factors may induce adult cardiomyocytes to enter the cell cycle in in vitro systems, 2,3 but in vivo this has been achieved only by genetic manipulation or by transfecting transcription factors. [4][5][6] On the basis that vascular endothelial growth factor (VEGF) receptors, usually considered to be exclusive of vascular endothelial cells, have been described in cultured rat cardiomyocytes, 7 and that this growth factor activates mitogen-activated protein kinases pathways, 8 we investigated if VEGF gene transfer to the heart may induce cardiomyocyte replication.…”

Cell Death in Acromegalic Cardiomyopathy

“…IGF-1 induces myocytes to reenter the cell cycle. 28,29 This growth factor activates cyclins and cyclin-dependent kinases in myocytes and cells enter the S-phase, replicating DNA. 29 In response to a sudden increase in ventricular loading, the myocyte IGF-1-IGF-1 receptor system is upregulated in vivo, 30 and this adaptation is coupled with enhanced induction and phosphorylation of cyclins and cyclin-dependent kinases.…”