Atrial Natriuretic Peptide - a regulatory protein in endothelial activation. Characterization of its in vivo anti-inflammatory action and the molecular targets involved
Zusammenfassung der Projektergebnisse
The project provided further infomiation on the anfi-inflammatory potential of the cardiovascular hormone ANP. We could clearly show ANP counteract endothelial leakage. We evaluated the precise in vivo relevance of this observation and, moreover, identified the permeability-controlling subcellular systems that are targeted by ANP. ANP inhibited changes of vascular endothelial (VE)-cadherin, ß-catenin, and p 120ctn morphology, VE-cadherin and myosin light chain 2 (MLC2) phosphorylation, and F-actin stress fiber formation. These changes seem to be predominantly mediated by the natriuretic peptide receptor (NPR)-A, but not by NPR-C. Thus we could highlight ANP as an interesting pharmacological compound opening new therapeutic options for preventing endothelial leakage. Unfortunately, we could not confirm our initial hypothesis that ANP affects LPS-induced inflammation in vivo in mice and were therefore forced to modify our working program as pointed out. In addition we could identify the CDK-inhibitor and anti-tumor agent roscovitine as an anti-inflammatory drug affecting the leukocyte-endothelial interaction as originally hypothesized for ANP.
Projektbezogene Publikationen (Auswahl)
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Atrial natriuretic peptide protects against histamine-induced endothelial barrier dysfunction in vivo. Mol. Pharmacol. 2008;74:1-8
Fürst R, Bubik MF, Bihari P, Mayer BA, Khandoga AG, Hoffmann F, Rehberg M, Krombach F, Zahler S, Vollmar AM
