gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

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Differential Effects of Vasodilatory Prostaglandins on Focal Adhesions, Cytoskeletal Architecture and Migration in Human Smooth Muscle Cells

Differentielle Wirkungen Vasodilatorischer Prostaglandine auf Fokale Adhäsionen, Zytoskelett und Migration

Meeting Abstract (Hypertonie 2004)

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  • presenting/speaker C. Bulin - Institut für Klinische Pharmakologie und Klinische Pharmakologie, Institut für Pathophysiologie (Düsseldorf, D)
  • presenting/speaker B. Levkau - Institut für Klinische Pharmakologie und Klinische Pharmakologie, Institut für Pathophysiologie (Düsseldorf, D)
  • presenting/speaker A.-A. Weber - Institut für Klinische Pharmakologie und Klinische Pharmakologie, Institut für Pathophysiologie (Düsseldorf, D)
  • presenting/speaker K. Schrör - Institut für Klinische Pharmakologie und Klinische Pharmakologie, Institut für Pathophysiologie (Düsseldorf, D)
  • presenting/speaker J.W. Fischer - Institut für Klinische Pharmakologie und Klinische Pharmakologie, Institut für Pathophysiologie (Düsseldorf, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP21

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/hoch2004/04hoch021.shtml

Published: August 10, 2005

© 2005 Bulin et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Objective: Cyclooxygenases 1 and -2 are expressed in atherosclerotic arteries and local generation of prostacyclin and prostaglandin E2 (PGE2) occurs. However, the role of cyclooxygenases and individual prostaglandins during plaque progression is currently uncertain. The present study characterizes the effect of vasodilatory prostaglandins on morphology, focal adhesion (FA) function and migration in human aortic smooth muscle cells (SMC).

Methods and results: The expression of prostacyclin receptor (IP) and the prostaglandin E (PGE) receptors 1, - 2, - 3 and - 4 (EP1-4) was verified by RT-PCR in SMC. FA and actin cytoskeleton were visualized by paxillin immunostaining and phalloidin staining. The stable prostacyclin analog, iloprost, transiently induced (i) disassembly of FA and stress fibers, (ii) partial retraction and rounding of SMC, (iii) hypophosphorylation of FA-kinase and paxillin as shown by immunoblotting and (iv) inhibition of platelet derived growth factor-BB induced migration in a modified boyden chamber assay. Inhibition of FAK-phosphorylation and morphological changes were mimicked by forskolin and inhibited by H89 and by the protein tyrosine phosphatase inhibitor vanadate. PGE2 was by far less efficient with respect to all parameters investigated. This difference correlated with the respective cAMP-induction in response to iloprost and PGE2.

Conclusion: Inhibition of FAK-phosphorylation and FA-function is a new target of vasodilatory prostaglandins, which might be causally involved in the anti-migratory effects of prostaglandins. The data also suggest that downstream of Gs-coupled prostaglandin receptors and cAMP/PKA the activation of a phosphatase mediates FAK-dephosphorylation. Importantly, prostacyclin analogs and PGE2 differ dramatically with respect to dephosphorylation of FAK and inhibition of migration, which might be of relevance for their respective functions in atherosclerosis.