Pulsatile stretch activates mitogen-activated protein kinase (MAPK) familymembers and focal adhesion kinase (p125(FAK)) in cultured rat cardiac myocytes

Recently, we demonstrated that pulsatile mechanical stretch induced rapid s ecretion of vascular endothelial growth factor (VEGF) by cultured rat cardi ac myocytes in vitro, To investigate whether pulsatile stretch activates in tracellular signaling in cardiac myocytes, we examined the activation of mi togen-activated protein kinase (MAPK) family members and focal adhesion kin ase (p125(FAK)) in cultured rat cardiac myocytes, We found that pulsatile s tretch rapidly phosphorylated p44/p42 MAPKs (extracellular signal-regulated protein kinase [ERK] 1/2), stress-activated protein kinase (SAPK), p38MAPK , and p125(FAK). Th, stretch-induced activation of ERKs was at least partly mediated by VEGF, which was shown to be induced by transforming growth fac tor (TGF)-beta, and was also partly dependent on tyrosine kinases as well a s protein kinase C (PKC), These data provide the direct evidence that pulsa tile stretch can activate intracellular signaling in cardiac myocytes and t hat this was at least partly mediated by VEGF, which may play a role in car diac adaptation to mechanical overload. (C) 1999 Academic Press.