AJP - Heart Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (April 21, 2006). doi:10.1152/ajpheart.01042.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
291/3/H1351    most recent
01042.2005v3
01042.2005v2
01042.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Akkawi, S.
Right arrow Articles by Higazi, A. A.-R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Akkawi, S.
Right arrow Articles by Higazi, A. A.-R.
Submitted on October 3, 2005
Accepted on January 31, 2006

LRP and {alpha}v{beta}3 mediate tPA-activation of smooth muscle cells

Sa'ed Akkawi1, Taher Nassar1, Mark Tarshis2, Douglas B. Cines3, and Abd Al-Roof Higazi4*

1 Clinical Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel
2 Interdepartmental Unit, Hebrew University-Hadassah Medical School, Jerusalem, Israel
3 Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States
4 Clinical Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel; Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States

* To whom correspondence should be addressed. E-mail: higazi{at}mail.med.upenn.edu.

Tissue-type plasminogen activator (tPA) regulates vascular contractility through the low-density lipoprotein-related receptor (LRP) and this effect is inhibited by plasminogen activator inhibitor-1 (PAI-1). We now report that tPA-mediated vasocontraction also requires the integrin {alpha}v{beta}3. tPA-induced contraction of rat aortic rings is inhibited by the RGD peptide and by monoclonal anti{alpha}v{beta}3 antibody. tPA induces the formation of a complex between LRP and {alpha}v{beta}3 in vascular smooth muscle cells. The three proteins are internalized within 10 minutes causing the cells to become refractory to re-addition of tPA. LRP and {alpha}v{beta}3 return to the cell surface by 90 minutes restoring cell responsiveness to tPA. PAI-1 and the PAI-1-derived hexapeptide EEIIMD abolish the vasocontracile activity of tPA and inhibit the tPA-mediated interaction between LRP and {alpha}v{beta}3. tPA induces calcium mobilization from intracellular stores in vascular smooth muscle cells and this effect is inhibited by PAI-1, RGD and antibodies to both LRP and {alpha}v{beta}3. These data indicate that tPA-mediated vasocontraction involves the coordinated interaction of LRP with {alpha}v{beta}3. Delineating the mechanism underlying these interactions and the nature of the signals transduced may provide new tools to regulate vascular tone and other consequences of tPA-mediated signaling.




This article has been cited by other articles:


Home page
 StrokeHome page
J. P. Lopez-Atalaya, B. D. Roussel, C. Ali, E. Maubert, K.-U. Petersen, V. Berezowski, R. Cecchelli, C. Orset, and D. Vivien
Recombinant Desmodus rotundus Salivary Plasminogen Activator Crosses the Blood-Brain Barrier Through a Low-Density Lipoprotein Receptor-Related Protein-Dependent Mechanism Without Exerting Neurotoxic Effects
Stroke, March 1, 2007; 38(3): 1036 - 1043.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. A. Eddy and A. B. Fogo
Plasminogen Activator Inhibitor-1 in Chronic Kidney Disease: Evidence and Mechanisms of Action
J. Am. Soc. Nephrol., November 1, 2006; 17(11): 2999 - 3012.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.