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Stimulation of endothelin-1 release by low density and very low density lipoproteins in cultured human endothelial cells

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      Abstract

      To examine the effects of lipoproteins on the secretion of endothelin-1 from endothelial cells, we measured immunoreactive (ir) endothelin-1 release from cultured human umbilical vein endothelial cells in the presence or absence of various concentrations of native low density lipoprotein (LDL), oxidized LDL, and very low density lipoprotein (VLDL). Cultured endothelial cells secreted ir-endothelin-1 into serum-free medium in a time-dependent manner, and the secretion was clearly stimulated following a 15–24-h incubation with 10 μg/ml oxidized LDL. The secretion of ir-endothelin-1 increased in a dose-dependent manner after a 24-h incubation with oxidized LDL, while only a high dose of native LDL and VLDL significantly increased ir-endothelin-1 secretion. The release of ir-endothelin-1 stimulated by 20 μg/ml oxidized LDL was reproduced by the same concentration of acetylated LDL but not native LDL. These observations indicate that the release of ir-endothelin-1 from endothelial cells is stimulated by lipoproteins, in particular by oxidized LDL, probably through the endothelial scavenger receptor. This increase in iendothelin-1 release induced by oxidized LDL may contribute to the development of atherosclerotic vascular lesions.

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      References

        • Haberland M.E.
        • Fogelman A.M.
        The role of altered lipoproteins in the pathogenesis of atherosclerosis.
        Am. Heart J. 1987; 113: 573
        • Steinberg D.
        • Parthasarathy S.
        • Carew T.E.
        • Khoo J.C.
        • Witztum J.L.
        Modifications of low-density lipoprotein that increase its atherogenicity.
        N. Engl. J. Med. 1989; 320: 915
        • Carew T.E.
        Role of biologically modified low-density lipoprotein in atherosclerosis.
        Am. J. Cardiol. 1989; 64: 18G
        • Ross R.
        • Glomset J.A.
        The pathogenesis of atherosclerosis.
        N. Engl. J. Med. 1976; 295: 369
        • Ross R.
        The pathogenesis of atherosclerosis: an update.
        N. Engl. J. Med. 1986; 314: 488
        • Schwartz S.M.
        • Heimark R.L.
        • Majesky M.W.
        Developmental mechanisms underlying pathology of arteries.
        Physiol. Rev. 1990; 70: 1177
        • Yanagisawa M.
        • Kurihara H.
        • Kimura S.
        • Tomobe Y.
        • Kobayashi M.
        • Mitsui Y.
        • Yazaki Y.
        • Goto K.
        • Masaki T.
        A novel potent vasoconstrictor peptide produced by vascular endothelial cells.
        Nature. 1988; 332: 411
        • Weissberg P.L.
        • Witchell C.
        • Davenport A.P.
        • Hesketh T.R.
        • Metcalfe J.C.
        The endothelin peptides ET-I, ET-2, ET-3 and sarafotoxin S6b are co-mitogenic with platelet-derived growth factor for vascular smooth muscle cells.
        Atherosclerosis. 1990; 85: 257
        • Lerman A.
        • Edwards B.S.
        • Hallett J.W.
        • Heublein D.M.
        • Sandberg S.M.
        • Burnett Jr., J.C.
        Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis.
        N. Engl. J. Med. 1991; 325: 997
        • Arendt R.M.
        • Wilbert-Lampen U.
        • Heucke L.
        Increased plasma endothelin in patients with hyperlipoproteinemia and stable or unstable angina (abstr.).
        Circulation. 1990; 82: III-248
        • Horio T.
        • Kohno M.
        • Murakawa K.
        • Yasunari K.
        • Yokokawa K.
        • Ueda M.
        • Takeda T.
        Increased plasma immunoreactive endothelin-1 concentration in hypercholesterolemic rats.
        Atherosclerosis. 1991; 89: 239
        • Kohno M.
        • Yasunari K.
        • Yokokawa K.
        • Murakawa K.
        • Horio T.
        • Takeda T.
        Inhibition by atrial and brain natriuretic peptides of endothelin-I secretion after stimulation with angiotensin II and thrombin of cultured human endothelial cells.
        J. Clin. Invest. 1991; 87: 1999
        • Kohno M.
        • Yasunari K.
        • Murakawa K.
        • Yokokawa K.
        • Horio T.
        • Fukui T.
        • Takada T.
        Release of immunoreactive endothelin from porcine aortic strips.
        Hypertension. 1990; 15: 718
        • Kohno M.
        • Yasunari K.
        • Murakawa K.
        • Yokokawa K.
        • Horio T.
        • Fukui T.
        • Takeda T.
        Plasma immunoreactive endothelin in essential hypertension.
        Am. J. Med. 1990; 88: 614
        • Wallenstein S.
        • Zucker C.L.
        • Fleiss J.L.
        Some statistical methods useful in circulation research.
        Circ. Res. 1980; 47: 1
        • Martin-Nizard F.
        • Houssaini H.S.
        • Lestavel-Delattre S.
        • Duriez P.
        • Fruchart J.
        Modified low density lipoproteins activate human macrophages to secrete immunoreactive endothelin.
        FEBS Lett. 1991; 293: 127
        • Boulanger C.
        • Hahn A.W.A.
        • Lüscher T.F.
        Oxidized low-density lipoproteins release endothelin from the human and porcine endothelium (abstr.).
        Circulation. 1990; 82: III-225
        • Kohno M.
        • Murakawa K.
        • Horio T.
        • Yokokawa K.
        • Yasunari K.
        • Fukui T.
        • Takeda T.
        Plasma immunoreactive endothelin-1 in experimental malignant hypertension.
        Hypertension. 1991; 18: 93
        • Emori T.
        • Hirata Y.
        • Ohta K.
        • Shichiri M.
        • Marumo F.
        Secretory mechanism of immunoreactive endothelin in cultured bovine endothelial cells.
        Biochem. Biophys. Res. Commun. 1989; 160: 93
        • Kohno M.
        • Murakawa K.
        • Yokokawa K.
        • Yasunari K.
        • Horio T.
        • Kurihara N.
        • Takeda T.
        Production of endothelin by cultured porcine endothelial cells: modulation by adrenaline.
        J. Hypertens. 1989; 7: S130
        • Kohno M.
        • Horio T.
        • Yokokawa K.
        • Kurihara N.
        • Takeda T.
        C-type natriuretic peptide inhibits thrombinand angiotensin II-stimulated endothelin release via cyclic guanosine 3′,5′-monophosphate.
        Hypertension. 1992; 19: 320
        • Boulanger C.
        • Lüscher T.F.
        Release of endothelin from the porcine aorta.
        J. Clin. Invest. 1990; 85: 587
        • Tanner F.C.
        • Noll G.
        • Boulanger C.M.
        • Lüscher T.F.
        Oxidized low density lipoproteins inhibit relaxations of porcine coronary arteries.
        Circulation. 1991; 83: 2012
        • Chin J.H.
        • Azhar S.
        • Hoffman B.B.
        Inactivation of endothelial derived relaxing factor by oxidized lipoproteins.
        J. Clin. Invest. 1992; 89: 10
        • Galle J.
        • Bassenge E.
        • Busse R.
        Oxidized low density lipoproteins potentiate vasoconstrictions to various agonists by direct interaction with vascular smooth muscle.
        Circ. Res. 1990; 66: 1287
        • Simon B.C.
        • Cunningham L.D.
        • Cohen R.A.
        Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.
        J. Clin. Invest. 1990; 86: 75
        • Komuro I.
        • Kurihara H.
        • Sugiyama T.
        • Takaku F.
        • Yazaki Y.
        Endothelin stimulates c fos and c-myc expression and proliferation of vascular smooth muscle cells.
        FEBS Lett. 1988; 238: 249
        • Hirata Y.
        • Takagi Y.
        • Fukuda Y.
        • Marumo F.
        Endothelin is a potent mitogen for rat vascular smooth muscle cells.
        Atherosclerosis. 1989; 78: 225
        • Bobik A.
        • Grooms A.
        • Millar J.A.
        • Mitchell A.
        • Grinpukel S.
        Growth factor activity of endothelin on vascular smooth muscle.
        Am. J. Physiol. 1990; 258: C408
        • Hessler J.R.
        • Robertson Jr., A.L.
        • Chisolm G.M.
        LDL-induced cytotoxicity and its inhibition by HDL in human vascular smooth muscle and endothelial cells in culture.
        Atherosclerosis. 1979; 32: 213
        • Hessler J.R.
        • Morel D.W.
        • Lewis L.J.
        • Chisolm G.M.
        Lipoprotein oxidation and lipoprotein-induce cytotoxicity.
        Arteriosclerosis. 1983; 32: 215
        • Block L.H.
        • Knorr M.
        • Vogt E.
        • Locher R.
        • Vetter W.
        • Groscurth P.
        • Qiao B.
        • Pometta D.
        • James R.
        • Regenass M.
        • Pletcher A.
        Low density lipoprotein causes general cellular activation with increased phosphatidylinositol turnover and lipoprotein catabolism.
        in: 3rd Edn. Proc. Natl. Acad. Sci. USA. 85. 1988: 885
        • Ishikawa Y.
        • Asaoka Y.
        • Taniguchi T.
        • Tsunemitsu M.
        • Fukuzaki H.
        Phosphatidylinositol turnover in human monocyte-derived macrophages by native and acetyl LDL.
        FEBS Lett. 1989; 246: 35
        • Sachinidis A.
        • Mengden T.
        • Locher R.
        • Brunner C.
        • Vetter W.
        Novel cellular activities for low density lipoprotein in vascular smooth muscle cells.
        Hypertension. 1990; 15: 704