The chromogranin A peptide vasostatin-I inhibits gap formation and signal transduction mediated by inflammatory agents in cultured bovine pulmonary and coronary arterial endothelial cells

Anna Blois, Boleslaw Srebro, Maurizio Mandalà, Angelo Corti, Karen B. Helle, Guldborg Serck-Hanssen

Research output: Contribution to journalArticle

Abstract

The proinflammatory agent tumour necrosis factor α (TNFα) is one of several agents causing vascular leakage. The N-terminal domain of CgA, vasostatin-I (CgA 1-76), has recently been reported to inhibit TNFα induced gap formation in human umbilical venous endothelial cells. Here we report on the effect of recombinant human CgA 1-78, vasostatin-I, on TNFα induced gap formation in two model systems of vascular leakage in arterial endothelial cells of bovine pulmonary (BPAEC) and coronary (BCAEC) origin. Vasostatin-I inhibited the TNFα induced gap formation in both models, being inactive in the unstimulated cells. The phosphorylation of p38MAP kinase in TNFα activated BPAEC was markedly attenuated in the presence of vasostatin-I and the inhibitory effect corresponded to that of the specific p38MAPK inhibitor SB203580. Vasostatin-I also inhibited the phosphorylation of p38MAPK induced by both thrombin and pertussis toxin in these cells. The results demonstrate that vasostatin-I has inhibitory effects on TNFα-induced disruption of confluent layers of cultured pulmonary and coronary arterial endothelial cells. This suggests that vasostatin-I may affect endothelial barrier dysfunction also in arterial vascular beds. Furthermore, the inhibitory activity of vasostatin-I may be associated with the p38MAPK signalling cascade via a pertussis toxin sensitive, presumably Gαi coupled mechanism.

Original languageEnglish
Pages (from-to)78-84
Number of pages7
JournalRegulatory Peptides
Volume135
Issue number1-2
DOIs
Publication statusPublished - Jul 15 2006

Keywords

  • Actin cytoskeleton reorganization
  • Arterial endothelium
  • p38MAPK
  • PTX
  • Recombinant human vasostatin-I (CgA )
  • Thrombin
  • TNFα

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Fingerprint Dive into the research topics of 'The chromogranin A peptide vasostatin-I inhibits gap formation and signal transduction mediated by inflammatory agents in cultured bovine pulmonary and coronary arterial endothelial cells'. Together they form a unique fingerprint.

  • Cite this