on September 30, 2004
Published online before print September 30, 2004, doi: 10.1161/01.ATV.0000146814.81581.68
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 19, 2004
Accepted on August 24, 2004
Differential Effects of Vasodilatory Prostaglandins on Focal Adhesions, Cytoskeletal Architecture, and Migration in Human Aortic Smooth Muscle Cells
C. Bulin ;
From the Molekulare Pharmakologie, Institut für Pharmakologie und Klinische Pharmakologie, Klinik für Gastroenterologie (C.B., U.A.), Hepatologie und Infektiologie, Heinrich Heine Universität Düsseldorf; Institut für Pathophysiologie (K.S.), Universitätsklinikum Essen, Germany.
* To whom correspondence should be addressed. E-mail: jens.fischer{at}uni-duesseldorf.de.
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 (SMCs).
Methods and Results--The stable prostacyclin analog iloprost transiently induced: (1) disassembly of FA and stress fibers, (2) partial retraction and rounding of SMCs, (3) hypophosphorylation of FA kinase (FAK) and paxillin, and (4) inhibition of platelet-derived growth factor-BB-induced migration. Inhibition of FAK phosphorylation and morphological changes were mimicked by forskolin, inhibited by H89, and prevented by the protein tyrosine phosphatase inhibitor vanadate and by calpeptin. 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 antimigratory effects of prostaglandins. 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.
Key words: focal adhesion kinase • extracellular matrix • prostaglandins • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  K. Sattler and B. Levkau Sphingosine-1-phosphate as a mediator of high-density lipoprotein effects in cardiovascular protection Cardiovasc Res, May 1, 2009; 82(2): 201 - 211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Pape, B. H. Rauch, A. C. Rosenkranz, G. Kaber, and K. Schror Transcriptional Inhibition of Protease-Activated Receptor-1 Expression by Prostacyclin in Human Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 534 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Bondesen, K. A. Jones, W. C. Glasgow, and G. K. Pavlath Inhibition of myoblast migration by prostacyclin is associated with enhanced cell fusion FASEB J, October 1, 2007; 21(12): 3338 - 3345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. E. Thomas, M. Peters-Golden, E. S. White, V. J. Thannickal, and B. B. Moore PGE2 inhibition of TGF-beta1-induced myofibroblast differentiation is Smad-independent but involves cell shape and adhesion-dependent signaling Am J Physiol Lung Cell Mol Physiol, August 1, 2007; 293(2): L417 - L428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Rauch, G. A. Scholz, D. Baumgartel-Allekotte, P. Censarek, J. W. Fischer, A.-A. Weber, and K. Schror Cholesterol Enhances Thrombin-Induced Release of Fibroblast Growth Factor-2 in Human Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): e20 - e25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Swaney, H. H. Patel, U. Yokoyama, B. P. Head, D. M. Roth, and P. A. Insel Focal Adhesions in (Myo)fibroblasts Scaffold Adenylyl Cyclase with Phosphorylated Caveolin J. Biol. Chem., June 23, 2006; 281(25): 17173 - 17179. [Abstract] [Full Text] [PDF]
|
|