Lipopolysaccharide augments expression and secretion of vascular endothelial growth factor in rat ventricular myocytes

Vascular endothelial growth factor (VEGF), also known as vascular permeabil ity factor, is highly expressed in the myocardium under various stimuli inc luding hypoxia and ischemia. On the other hand, lipopolysaccharide (LPS) ca uses systemic inflammatory response syndrome (SIRS), which consists of syst emic pathophysiological changes related to vascular hyperpermeability. To t est the hypothesis that VEGF is one of the important mediators of SIRS, we examined effects of LPS on the VEGF expression and secretion in cultured ne onatal rat ventricular myocytes, LPS (10 mu g/ml) rapidly (within 1 h) augm ented the levels of VEGF mRNA in these cells. Pharmacological inhibition of nucleic factor-kappa B or tyrosine kinases did not affect the LPS-induced augmentation of VEGF mRNA expression, while these treatments markedly suppr essed the up-regulation of inducible nitric oxide synthase (iNOS) expressio n by LPS, The VEGF concentrations in the conditioned media were also signif icantly increased by the LPS treatment of 6 h, in conclusion, LPS augments VEGF expression and secretion in rat ventricular myocytes, suggesting that VEGF may be involved in pathogenesis of SIRS, LPS may induce VEGF mRNA thro ugh the signaling pathways that are distinct from those responsible for the iNOS induction. (C) 2000 Academic Press.