title: Lipopolysaccharide augments expression and secretion of vascular endothelial growth factor in rat ventricular myocytes.
abstract: Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is highly expressed in the myocardium under various stimuli including hypoxia and ischemia. On the other hand, lipopolysaccharide (LPS) causes systemic inflammatory response syndrome (SIRS), which consists of systemic pathophysiological changes related to vascular hyperpermeability. To test 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 neonatal rat ventricular myocytes. LPS (10 microg/ml) rapidly (within 1 h) augmented the levels of VEGF mRNA in these cells. Pharmacological inhibition of nucleic factor-kappaB or tyrosine kinases did not affect the LPS-induced augmentation of VEGF mRNA expression, while these treatments markedly suppressed the up-regulation of inducible nitric oxide synthase (iNOS) expression by LPS. The VEGF concentrations in the conditioned media were also significantly 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 through the signaling pathways that are distinct from those responsible for the iNOS induction.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sugishita
authors.forename: T
authors.initials: T
authors.lastname: Shimizu
authors.forename: A
authors.initials: A
authors.lastname: Yao
authors.forename: K i
authors.initials: Ki
authors.lastname: Kinugawa
authors.forename: T
authors.initials: T
authors.lastname: Nojiri
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: H
authors.initials: H
authors.lastname: Matsui
authors.forename: R
authors.initials: R
authors.lastname: Nagai
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000378:metabolism; D004790:Enzyme Induction; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008222:Lymphokines / Q000096:biosynthesis* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D017077:Culture Media, Conditioned; D016228:Endothelial Growth Factors; D008070:Lipopolysaccharides; D008222:Lymphokines; D016328:NF-kappa B; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D011505:Protein-Tyrosine Kinases