Involvement of Cyclooxygenase- and Lipoxygenase-Mediated Conversion of Arachidonic Acid in Controlling Human Vascular Smooth Muscle Cell Proliferation

Herm-Jan M Brinkman; Marijke F van Buul-Worteiboer; Jan A van Mourik

doi:10.1055/s-0038-1645212

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1990; 63(02): 291-297
DOI: 10.1055/s-0038-1645212

Original Article

Schattauer GmbH Stuttgart

Involvement of Cyclooxygenase- and Lipoxygenase-Mediated Conversion of Arachidonic Acid in Controlling Human Vascular Smooth Muscle Cell Proliferation

Herm-Jan M Brinkman

The Central Laboratory of the Netherlands Red Cros Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands

,

Marijke F van Buul-Worteiboer

The Central Laboratory of the Netherlands Red Cros Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands

,

Jan A van Mourik

The Central Laboratory of the Netherlands Red Cros Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Amsterdam, The Netherlands

› Author Affiliations

Abstract

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Summary

We observed that the growth of human umbilical arterysmooth muscle cells was inhibited by the phospholipase A₂ inhibitors p-bromophenacylbromide and mepacrine. Thesefindings suggest that fatty acid metabolism might be integrated in the control mechanism of vascular smooth muscle cell proliferation. To identify eicosanoids possibly involved in this process, we studied both the metabolism of arachidonic acid of these cells in more detail and the effect of certain arachidonic acid metabolites on smooth muscle cells growth. We found no evidence for the conversion of arachidonic acid via the lipoxygenase pathway. In contrast, arachidonic acid was rapidly converted via the cyclooxy-genase pathway. The following metabolites were identified: prostaglandin E₂ (PGE₂), 6-keto-prostaglandin F_1α (6-k-PGF_1α), prostaglandin F_2α (PGF_2α), 12-hydroxyheptadecatrienoic acid (12-HHT) and 11-hydroxyeicosatetetraenoic acid (11-HETE). PGE₂ was the major metabolite detected. Arachidonic acid metabolites were only found in the culture medium, not in the cell. After synthesis, 11-HETE was cleared from the culture medium. We have previously reported that PGE₂ inhibits the serum-induced [³H]-thymidine incorporation of growth-arrested human umbilical artery smooth muscle cells. Here we show that also 11-HETEexerts this inhibitory property. Thus, our data suggeststhat human umbilical artery smooth muscle cells convert arachidonic acid only via the cyclooxygenase pathway. Certain metabolites produced by this pathway, including PGE₂ and 11-HETE, may inhibit vascular smooth muscle cell proliferation.

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References

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