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      Inhibition by Eicosapentaenoic Acid of Oxidized-LDL- and Lysophosphatidylcholine-Induced Human Coronary Artery Smooth Muscle Cell Production of Endothelin

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          The objectives of the present study were (1) to determine whether oxidized low-density lipoprotein (LDL) and lysophosphatidylcholine (lyso-PC), a major phospholipid component of oxidized LDL, stimulate the production of endothelin-1 (ET)-1 in cultured human coronary artery smooth muscle cells (SMCs), and (2) to examine the possible effect of an antiatherogenic agent, eicosapentaenoic acid (EPA), on oxidized-LDL- and lyso-PC-stimulated ET-1 production in these cells. Oxidized LDL (10–50 µg/ml) and lyso-PC (10<sup>–7</sup> to 10<sup>–5</sup> mol/l) stimulated ET-1 production in a concentration-dependent manner. By contrast, the effects of native LDL and phosphatidylcholine were modest or absent. Lyso-PC (10<sup>–7</sup> to 10<sup>–5</sup> mol/l) and oxidized LDL (10–50 µg/ml) significantly induced particulate protein kinase C (PKC) activation. Lyso-PC- and oxidized-LDL-stimulated ET-1 production was significantly inhibited by PKC inhibitor, PKC (19–36). EPA (80–160 µmol/l) clearly suppressed ET-1 production stimulated by oxidized LDL and lyso-PC in a concentration-dependent manner. Furthermore, EPA (160 µmol/l) significantly inhibited lyso-PC (10<sup>–5</sup> mol/l)- and oxidized LDL (50 µg/ml)-induced particulate PKC activation. Results suggest that oxidized LDL and lyso-PC stimulate ET-1 production by a mechanism involving activation of PKC, and that EPA suppresses ET-1 production stimulated by lyso-PC as well as oxidized LDL probably through the modulation of PKC in human coronary artery SMCs. EPA may exert an antiatherosclerotic effect, in part, through these mechanisms.

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          Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins.

          Atherosclerosis in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators--agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor). Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium. Recently, 'cell-modified' or 'oxidized' low-density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators.
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            Oxidized Low Density Lipoprotein and Lysophosphatidylcholine Stimulate Cell Cycle Entry in Vascular Smooth Muscle Cells

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              • Abstract: not found
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              Involvement of protein kinase C in the supersensitivity to 5-HT caused by oxidized low-density lipoproteins


                Author and article information

                J Vasc Res
                Journal of Vascular Research
                S. Karger AG
                August 2001
                11 July 2001
                : 38
                : 4
                : 379-388
                aSecond Department of Internal Medicine, Kagawa Medical University School of Medicine, Kagawa, Japan; bDepartment of Medicine, Wright State University/VA Medical Center, Dayton, Ohio, USA
                51069 J Vasc Res 2001;38:379–388
                © 2001 S. Karger AG, Basel

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                Page count
                Figures: 8, Tables: 3, References: 49, Pages: 10
                Research Paper


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