Donate Help Contact The AHA Sign In Home
American Heart Association
Arteriosclerosis, Thrombosis, and Vascular Biology
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Arteriosclerosis, Thrombosis, and Vascular Biology. 1994;14:1047-1055

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
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
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mullins, D. E.
Right arrow Articles by Davis, H. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mullins, D. E.
Right arrow Articles by Davis, H. R.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH

Arteriosclerosis and Thrombosis, Vol 14, 1047-1055, Copyright © 1994 by American Heart Association

ARTICLES

Inhibition of PDGF receptor binding and PDGF-stimulated biological activity in vitro and of intimal lesion formation in vivo by 2- bromomethyl-5-chlorobenzene sulfonylphthalimide

DE Mullins, F Hamud, R Reim and HR Davis
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539.

The proliferation of vascular smooth muscle cells (SMCs) is a key event in the development of atherosclerotic lesions and in the restenosis of arteries after angioplasty. Polypeptide growth factors are potent SMC mitogens in vitro and are believed to be involved in SMC proliferation in vivo. Strong data exist linking platelet-derived growth factor (PDGF) activity to human atherosclerosis. However, no low-molecular- weight antagonists of this growth factor have been discovered. We identified a compound, SCH 13929 (2-bromomethyl-5-chlorobenzene sulfonylphthalimide), which inhibits binding of 125I-PDGF BB to cell surface receptors with an IC50 of 0.13 mumol/L. This compound has a lesser effect on the binding of 125I-epidermal growth factor (EGF), 125I-basic fibroblast growth factor (bFGF), or 125I-endothelin to specific cell surface receptors. Exposure of cultured SMCs to SCH 13929 inhibits PDGF BB- and PDGF AA-stimulated DNA synthesis but not EGF- or bFGF-stimulated DNA synthesis. PDGF BB-stimulated SMC division is also inhibited by exposure to SCH 13929. Chemotaxis assays indicate that SCH 13929 inhibits PDGF-stimulated directional migration and suggest that the compound interacts with PDGF rather than with the receptor. Oral administration of SCH 13929 (100 mg/kg per day) to Sprague-Dawley rats or spontaneously hypertensive rats results in significant inhibition of lesion formation in the balloon catheter-deendothelialized carotid artery. These results suggest that SCH 13929 may be a useful tool for understanding the role of PDGF in intimal lesion formation.


This article has been cited by other articles:


Home page
 J Am Coll CardiolHome page
B. Chandrasekar and J.-F. Tanguay
Platelets and restenosis
J. Am. Coll. Cardiol., March 1, 2000; 35(3): 555 - 562.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
C.-H. Heldin and B. Westermark
Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor
Physiol Rev, October 1, 1999; 79(4): 1283 - 1316.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
D. Bönisch, A.-A. Weber, M. Wittpoth, M. Osinski, and K. Schrör
Antimitogenic Effects of Trapidil In Coronary Artery Smooth Muscle Cells by Direct Activation of Protein Kinase A
Mol. Pharmacol., August 1, 1998; 54(2): 241 - 248.
[Abstract] [Full Text]

Home page
 CirculationHome page
J. Waltenberger
Modulation of Growth Factor Action : Implications for the Treatment of Cardiovascular Diseases
Circulation, December 2, 1997; 96(11): 4083 - 4094.
[Abstract] [Full Text]


ATVB Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 1994 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.