Skip Navigation

Cardiovascular Research 2000 47(4):749-758; doi:10.1016/S0008-6363(00)00129-2
© 2000 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters 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 Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Underwood, P.A.
Right arrow Articles by Mitchell, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Underwood, P.A.
Right arrow Articles by Mitchell, S. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2000, European Society of Cardiology

Low density lipoproteins in human plasma make vascular smooth muscle cells resistant to growth inhibition by heparin

P.A. Underwood* and Sue M. Mitchell

CSIRO Molecular Science, 2 Richardson Place, Riverside Corporate Park, Delhi Rd, PO Box 184, N. Ryde, NSW 2113, Australia

* Corresponding author. Tel.: +61-2-9490-5000; fax: +61-2-9490-5005 anne.underwood{at}molsci.csiro.au

Objective: Vascular smooth muscle cell hyperplasia plays a role in atherosclerosis and restenosis. While heparin has shown promise as an inhibitor of smooth muscle cell proliferation in vitro and in some animal models, it has failed to reduce restenosis in clinical trials. We have previously shown that human smooth muscle cells grown in the presence of human serum are heparin resistant, whereas in the presence of bovine serum they are heparin sensitive. In this report, we demonstrate that the heparin resistance factor is present in human plasma as well as serum, and characterise it further. Methods: Human vascular smooth muscle cells were cultured as explants from the media of redundant adult internal mammary or umbilical cord arteries. They were tested for sensitivity to heparin at 100 µg/ml in the growth medium, in the presence of foetal bovine serum, human-plasma-derived serum, human whole blood serum, or fractions derived from these. Results: In the presence of foetal bovine serum, heparin inhibited cell proliferation, while human-plasma-derived or whole blood sera conveyed heparin resistance. This activity was contained within the fraction of plasma/serum which bound to heparin Sepharose, and the sub-fraction which was retained by a membrane filter of molecular weight cut off of 100 000. All the heparin resistance in this latter fraction was supplied by lipoproteins. LDL prepared directly from human plasma conveyed similar heparin resistance to the lipoproteins from the above sub-fraction. Conclusion: LDL in human plasma/serum conveys resistance to the anti-proliferative effects of heparin upon vascular smooth muscle cells. This activity may interfere with potential therapeutic effects of heparin as an anti-restenosis agent.

KEYWORDS Atherosclerosis; Cell culture/isolation; Growth factors; Lipoproteins; Restenosis; Smooth muscle


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 FASEB J.Home page
I. GOUNI-BERTHOLD and A. SACHINIDIS
Does the coronary risk factor low density lipoprotein alter growth and signaling in vascular smooth muscle cells?
FASEB J, October 1, 2002; 16(12): 1477 - 1487.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.