Stimulation of arterial endothelial cell prostacyclin synthesis by high density lipoproteins.

L N Fleisher,A R Tall,L D Witte,R W Miller,P J Cannon

doi:10.1016/s0021-9258(18)34477-6

L N Fleisher, A R Tall + Show 3 more

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https://doi.org/10.1016/s0021-9258(18)34477-6

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Journal: The Journal of biological chemistry	Publication Date: Jun 1, 1982
Citations: 275	License type: cc-by

Abstract

Prostacyclin (PGI2) is a vasoactive prostaglandin synthesized by vascular endothelial and smooth muscle cells. In order to investigate whether plasma lipoproteins influence the biosynthesis and release of prostacyclin by vascular tissues, human high density lipoproteins (HDL) and low density lipoproteins (LDL) were incubated with porcine arterial endothelial cells grown in tissue culture. PGI2 production was measured by radioimmunoassay of its stable metabolite, 6-keto-PGF1 alpha. In incubations of HDL with endothelial cells for 24 h, levels of 6-keto-PGF1 alpha in the medium increased significantly in a dose-dependent fashion to values 5-fold above control. This effect was less pronounced in confluent than in subconfluent cultures and did not occur in the presence of an inhibitor of cyclooxygenase. No significant stimulation of 6-keto-PGF1 alpha was observed when the endothelial cells were incubated with LDL. In time course experiments with HDL, 6-keto-PGF1 alpha levels increased continuously over 24 h. Rat HDL, containing a high content of arachidonate in its cholesterol ester fatty acids, caused a 2-4-fold greater release of 6-keto-PGF1 alpha than human HDL. The delipidated apoprotein of both human and rat HDL caused similar stimulation of 6-keto-PGF1 alpha production, but much less than intact HDL. The data indicate that HDL stimulates PGI2 synthesis by cultured arterial endothelial cells, possibly by providing the cells with arachidonate.

Highlights

The datafrom 4 experiments are summarized in Fig. 1.The concentration of 6-keto-PGF1, in the medium of control endothelial cell cultures was 2.4 f 0.03ng/ml at 24 h
When endothelial cells were incubated with media containing human HDL, the production of 6-keto-PGF1, was stimulated 5-fold ( p < 0.01)
Medium from endothelial cells incubated with human LDL at two concentrations (0.15 and 0.015 mg of cholesterol/ml) did not contain significantly increased concentrations of 6-keto-PGFi,(Fig. 1).Cells incubated in medium with sodium arachidonate (5and 10p ~als)o produced Significantly more 6-keto-PGFj, than control cells (Fig. 1).Indomethacin inhibited completely the stimulation of 6-keto-PGF1, by HDL and by sodium arachidonate (Fig. 1)

Summary

Introduction

The datafrom 4 experiments are summarized in Fig. 1.The concentration of 6-keto-PGF1, in the medium of control endothelial cell cultures was 2.4 f 0.03ng/ml at 24 h. When endothelial cells were incubated with media containing human HDL, the production of 6-keto-PGF1, was stimulated 5-fold ( p < 0.01). Medium from endothelial cells incubated with human LDL at two concentrations (0.15 and 0.015 mg of cholesterol/ml) did not contain significantly increased concentrations of 6-keto-PGFi,,(Fig. 1).Cells incubated in medium with sodium arachidonate (5and 10p ~als)o produced Significantly more 6-keto-PGFj, than control cells (Fig. 1).Indomethacin inhibited completely the stimulation of 6-keto-PGF1, by HDL and by sodium arachidonate (Fig. 1).

Results

Conclusion