Ciprostene, a prostacyclin analog, suppresses human smooth muscle cells from primary but not restenotic coronary lesions

J. Benjamin Craven, Steven R. Bailey, Jian Luo, Eugene Sprague

Research output: Contribution to journalArticle

Abstract

Restenosis is a major limitation of percutaneous revascularization with smooth muscle cell (SMC) proliferation playing a primary role. Prostacyclin inhibits SMC growth in vitro but its short half-life limits its use. Ciprostene (CIP), a stable analog, reportedly inhibits the proliferation of bovine aortic (Ao) SMCs. Whether CIP affects the growth of human SMCs in culture is unknown. Accordingly, we examined whether CIP inhibits Ao SMC growth in vitro, as well as its effects on human coronary SMCs derived from either primary or restenotic atherosclerotic lesions harvested by directional coronary atherectomy. After establishing the cells in culture, SMC were seeded at 4 × 10s/cm2 and grown in medial (M199+10% fetal calf serum) containing CIP at concentrations between 0 and 50 uM. Cell counts were quantified using Coulter counter methods over 16 days. Results: Ao SMC growth was completely inhibited by CIP at concentrations of 50uM relative to untreated SMC. Of note, while SMCs obtained from primary coronary lesions were inhibited by approximately 50% when grown in concentrations of 50 uM CIP, growth of SMCs from restenotic lesions were not inhibited. We conclude: CIP is efficacious in inhibiting human Ao SMCs. In addition, CIP reduced growth of SMCs from primary coronary lesions, but was ineffective in inhibiting cells derived from restenotic lesions. Thus, though prostacyclin plays a Key role in human Ao SMC growth, cells from restenotic atherosclerotic lesions appear to be insensitive to this agent. Explanation of these differences may aid in the development of therapeutic strategies to reduce restenosis.

Original languageEnglish (US)
Pages (from-to)102A
JournalJournal of Investigative Medicine
Volume44
Issue number1
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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