Nitric oxide inhibition of endothelial cell mitogenesis and proliferation

Rajabrata Sarkar, R Clinton Webb, James C. Stanley

Research output: Contribution to journalArticle

66 Citations (Scopus)

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 - Jan 1 1995

Fingerprint

S-Nitroso-N-Acetylpenicillamine
Nitric Oxide
Endothelial Cells
Cell Proliferation
Nitric Oxide Donors
Smooth Muscle Myocytes
DNA
S Phase
Thymidine
Glutathione
Blood Vessels
Canidae
Cell Count
Wounds and Injuries
1,1-diethyl-2-hydroxy-2-nitrosohydrazine
1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole
spermine nitric oxide complex

ASJC Scopus subject areas

  • Surgery

Cite this

Nitric oxide inhibition of endothelial cell mitogenesis and proliferation. / Sarkar, Rajabrata; Webb, R Clinton; Stanley, James C.

In: Surgery, Vol. 118, No. 2, 01.01.1995, p. 274-279.

Research output: Contribution to journalArticle

Sarkar, Rajabrata ; Webb, R Clinton ; Stanley, James C. / Nitric oxide inhibition of endothelial cell mitogenesis and proliferation. In: Surgery. 1995 ; Vol. 118, No. 2. pp. 274-279.
@article{baddf7ccf8ae427295189d8633ada122,
title = "Nitric oxide inhibition of endothelial cell mitogenesis and proliferation",
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.",
author = "Rajabrata Sarkar and Webb, {R Clinton} and Stanley, {James C.}",
year = "1995",
month = "1",
day = "1",
doi = "10.1016/S0039-6060(05)80334-4",
language = "English (US)",
volume = "118",
pages = "274--279",
journal = "Surgery (United States)",
issn = "0039-6060",
publisher = "Mosby Inc.",
number = "2",

}

TY - JOUR

T1 - Nitric oxide inhibition of endothelial cell mitogenesis and proliferation

AU - Sarkar, Rajabrata

AU - Webb, R Clinton

AU - Stanley, James C.

PY - 1995/1/1

Y1 - 1995/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0029156792&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029156792&partnerID=8YFLogxK

U2 - 10.1016/S0039-6060(05)80334-4

DO - 10.1016/S0039-6060(05)80334-4

M3 - Article

C2 - 7638744

AN - SCOPUS:0029156792

VL - 118

SP - 274

EP - 279

JO - Surgery (United States)

JF - Surgery (United States)

SN - 0039-6060

IS - 2

ER -