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;14:254-260

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
Right arrow Citation Map
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 Hedin, U.
Right arrow Articles by Swedenborg, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hedin, U.
Right arrow Articles by Swedenborg, J.

Arteriosclerosis and Thrombosis, Vol 14, 254-260, Copyright © 1994 by American Heart Association

ARTICLES

Antithrombin III inhibits thrombin-induced proliferation in human arterial smooth muscle cells

U Hedin, S Frebelius, J Sanchez, M Dryjski and J Swedenborg
Department of Experimental Surgery, Karolinska Hospital, Stockholm, Sweden.

Thrombin has attracted increasing attention as a possible mitogen for vascular smooth muscle cells in lesion development both after vascular injury and in atherogenesis. In this study, the ability of antithrombin III to inhibit alpha-thrombin-induced DNA synthesis and cell proliferation in human arterial smooth muscle cells was analyzed. We demonstrate a concentration-dependent initiation of DNA synthesis and cell proliferation by alpha-thrombin. This effect was abolished when complex formation with antithrombin III was allowed before thrombin was added to the cell cultures. Addition of alpha-thrombin and antithrombin III simultaneously at the beginning of the incubation period also resulted in an inhibition of thrombin-induced DNA synthesis, but to a lower degree. The inhibitory activity of antithrombin III was enhanced in the presence of heparin, which on its own had no inhibitory effect on thrombin-induced DNA synthesis. In contrast, the mitogenic activity of alpha-thrombin could be inhibited by heparin in the presence of low concentrations of serum. This inhibition was dependent on the presence of antithrombin III in serum, since heparin lacked effect if antithrombin III was depleted from serum by immunoaffinity chromatography. Analysis of the enzymatic activity of thrombin showed that the influence on catalytic activity of thrombin corresponded to the mitogenic activity of thrombin in the presence of heparin, antithrombin III, and serum. The results suggest that the mitogenic activity of thrombin is regulated by antithrombin III. Therefore, antithrombin III may serve dual functions by inhibiting thrombin in the coagulation cascade and by neutralizing its growth-promoting effects on vascular smooth muscle cells.


This article has been cited by other articles:


Home page
 Eur Heart JHome page
J Wohrle, E Al-Khayer, U Grotzinger, C Schindler, M Kochs, V Hombach, and M Hoher
Comparison of the heparin coated vs the uncoated Jostent(R)--no influence on restenosis or clinical outcome
Eur. Heart J., October 1, 2001; 22(19): 1808 - 1816.
[Abstract] [PDF]

Home page
 J Am Coll CardiolHome page
W. H. Matthai Jr., P. B. Kurnik, W. C. Groh, W. J. Untereker, and J. E. Siegel
Antithrombin activity during the period of percutaneous coronary revascularization: Relation to heparin use, thrombotic complications and restenosis
J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1248 - 1256.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
N. N. Kahn, W. A. Bauman, and A. K. Sinha
Demonstration of a novel circulating anti-prostacyclin receptor antibody
PNAS, August 5, 1997; 94(16): 8779 - 8782.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
C. Gerdes, V. Faber-Steinfeld, O. Yalkinoglu, and S. Wohlfeil
Comparison of the Effects of the Thrombin Inhibitor r-Hirudin in Four Animal Models of Neointima Formation After Arterial Injury
Arterioscler Thromb Vasc Biol, October 1, 1996; 16(10): 1306 - 1311.
[Abstract] [Full Text]

Home page
 Circ. Res.Home page
G. Fager
Thrombin and Proliferation of Vascular Smooth Muscle Cells
Circ. Res., October 1, 1995; 77(4): 645 - 650.
[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.