Effect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury

Blazer R. Edelman, David H. Adams, Morris J. Karnovsky

Research output: Contribution to journalArticlepeer-review

227 Scopus citations


Continuous intravenous infusion of heparin suppresses smooth muscle cell proliferation in rats after endothelial injury but may lead to hemorrhage and other complications. The anticoagulant property has been removed from chemically modified heparin without loss of antiproliferative effect but use of such compounds is still limited. In this study ethylene-vinyl acetate copolymer matrices containing standard and modified heparin were placed adjacent to rat carotid arteries at the time of balloon dendothelialization. After 14 days arterial occlusion by smooth muscle cell proliferation was defined. Matrix delivery of both heparin compounds effectively diminished this proliferation in comparison to controls without producing systemic anticoagulation or side effects. In addition, this mode of therapy appeared more effective than the administration of the same agents by either intravenous pumps or heparin/polymer matrices placed in a subcutaneous site distant from the injured carotid artery. Thus, heparin's inhibition of smooth muscle cell proliferation after vascular injury might be most effective within the microenvironment of the injured vessel wall, and the accelerated atherosclerosis or restenosis that often follows angioplasty and other vascular interventions might best be treated with site-specific therapy.

Original languageEnglish
Pages (from-to)3773-3777
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - 1990
Externally publishedYes


  • Angioplasty
  • Atherosclerosis
  • Polymer-based controlled delivery
  • Vascular injury
  • Vascular surgery


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