Protein kinase C-b mediates lipoprotein-induced generation of PAI-1 from vascular endothelial cells

نویسندگان

  • SONG REN
  • GARRY X. SHEN
  • Garry X. Shen
چکیده

Ren, Song, Shalini Shatadal, and Garry X. Shen. Protein kinase C-b mediates lipoprotein-induced generation of PAI-1 from vascular endothelial cells. Am J Physiol Endocrinol Metab 278: E656–E662, 2000.—Elevated levels of low-density lipoproteins (LDL) and lipoprotein(a) [Lp(a)] have been considered strong risk factors for atherosclerotic cardiovascular disease. Increased production of plasminogen activator inhibitor-1 (PAI-1) has been implicated in the development of thrombosis and atherosclerosis. Previous studies by our group and others demonstrated that oxidation enhances LDLand Lp(a)-induced production of PAI-1 in human umbilical vein endothelial cells (HUVEC). The present study examined the involvement of protein kinase C (PKC) and its isoform in vascular endothelial cells (EC) induced by native or oxidized LDL and Lp(a). Treatment with Lp(a) or LDL transiently increased PKC activity at 15 min and 5.5 h after the start of lipoprotein treatment in EC. Copper-oxidized LDL and Lp(a) induced greater PKC activation in EC compared with comparable forms of those lipoproteins. Additions of 1 μM calphostin C, a PKC-specific inhibitor, at the beginning or $5 h, but not $9 h, after the initiation of lipoprotein treatment, blocked native and oxidized LDLor Lp(a)-induced increases in PKC activity and PAI-1 production. Treatment of LDL, Lp(a), or their oxidized forms was induced in translocation of PKC-b1 from cytosol to membrane in HUVEC. Treatments with 60 nM 379196, a PKC-b-specific inhibitor, effectively prevented PAI-1 production induced by LDL, Lp(a), or their oxidized forms in HUVEC and human coronary artery EC. The results suggest that activation of PKC-b may mediate the production of PAI-1 in cultured arterial and venous EC induced by LDL, Lp(a), or their oxidized forms.

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تاریخ انتشار 2000