Integrin-Dependent and -Independent Signaling During Pressure-Overload Cardiac Hypertrophy

摘要: In an attempt to uncover the linkage between hemodynamic load and cardiac hypertrophy, we focused on cytoskeletal (CSK) assembly of signaling proteins in pressure-overloaded feline myocardium. Analysis showed CSK association c-Src, β3-integrin, FAK, PTP-1B, p130Cas 4 48 hour pressure overloaded (PO) This was accompanied by increased amounts both total fibronectin (FN) vitronectin (VN) their attachment cardiocyte sarcolemma, indicating that a change extracellular matrix (ECM) composition might be responsible for these proteins. Furthermore, analysis with adult cardiocytes cultured three-dimensional (3-D) gel made either collagen containing FN VN or agarose alone 12 hours revealed some only matrix, event could blocked RGD peptide. To investigate role CSK-assembled proteins, activation two S6 kinase (S6K) isoforms, p70S6K p85S6K, are involved translational transcriptional measured PO While isoforms activated substantially, occurred maximally at 1 overload prior The S6K found mediated PI 3-kinase-independent pathway possible involvement protein C. studies performed vitro embedding gels stimulating them electrically contract types gels, although present matrix. Therefore, demonstrate activates integrin-dependent -independent signaling, which results, respectively, recruitment activation. Both may play critical roles hypertrophic growth regulation.