Nitric oxide inhibition of endothelial cell mitogenesis and proliferation

Rajabrata Sarkar, R. Clinton Webb, James C. Stanley

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Background Endothelial cell (EC) proliferation is essential in vascular repair after injury to the vessel wall. Impaired EC proliferation may be an important factor contributing to vessel wall disease. Nitric oxide (NO) inhibits proliferation of many cells, including smooth muscle cells (SMC). We tested the hypotheis that NO inhibits EC proliferation and DNA synthesis. Methods Cultured canine venous ECs were treated with NO donors: S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-glutathione (GSNO), or spermine NONOate (SP NO). Proliferation was determined by cell counts after 48 hours. Parallel proliferation studies were done with rat aortic SMC. ECs synchronized in S phase were treated with the NO donor diethylamine NONOate (DEA NO), and DNA synthesis was measured as the incorporation of tritiated thymidine, A NO antagonist, cPTIO, was used to reverse the effects of DEA NO. Results. Concentration-dependent (1 to 100 mmol/L) inhibition of EC proliferation (11% to 71% inhibition; p<0.05) was seen with SNAP. Similar inhibition of proliferation was noted with the NO donors GSNO and SP NO and in SMC treated with SNAP. DEA NO caused concentration-dependent (0.1 to 1 mmol/L) inhibition of EC DNA synthesis (39% to 85% inhibition; p<0.05), which was reversed by cPTIO. Conclusions. NO inhibits proliferation and mitogenesis of cultured ECs. This may occur in certain pathologic states, where production of NO in plaques and diseased vessels impedes reendothelialization, thus contributing to adverse thrombotic and vasospastic events.

Original languageEnglish (US)
Pages (from-to)274-279
Number of pages6
JournalSurgery
Volume118
Issue number2
DOIs
StatePublished - Aug 1995

ASJC Scopus subject areas

  • Surgery

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