Inhibitory Mechanisms of Low Concentrations of Oxidized Low-Density Lipoprotein on Platelet Aggrigation

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題名:	Inhibitory Mechanisms of Low Concentrations of Oxidized Low-Density Lipoprotein on Platelet Aggrigation
作者:	蔡妍菊;蕭哲志;陳增福;周敦穗 Chou DS;Chan CH;Hsiao G;Shen MY;Tsai YJ;Chen TF;Sheu JR
貢獻者:	醫學院藥理學系
日期:	2006
上傳時間:	2009-10-07 14:51:10 (UTC+8)
摘要:	The intracellular mechanisms underlying oxidized low-density lipoprotein (oxLDL)-signaling pathways in platelets are not yet completely understood. Therefore, the aim of this study was to further examine the effects of oxLDL in prevention of platelet aggregation. In this study, oxLDL concentration-dependently (40–120 \upmuUnknown control sequence '\upmu'g/ml) inhibited platelet aggregation in human platelet-rich plasma stimulated by agonists. Moreover, oxLDL (40 and 80 \upmuUnknown control sequence '\upmu'g/ml) markedly decreased the fluorescence intensity of platelet membranes tagged with diphenylhexatriene. Rapid phosphorylation of a protein of Mr 47,000 (P47), a marker of protein kinase C activation, was triggered by PDBu (150 nM). This phosphorylation was markedly inhibited by oxLDL (40 and 80 \upmuUnknown control sequence '\upmu'g/ml) in phosphorus-32-labeled platelets. In addition, oxLDL (40 and 80 \upmuUnknown control sequence '\upmu'g/ml) markedly increased levels of cyclic AMP and cyclic AMP-induced vasodilator-stimulated phosphoprotein (VASP) Ser157 phosphorylation. The thrombin-evoked increase in pHi was inhibited in the presence of oxLDL (40 and 80 \upmuUnknown control sequence '\upmu'g/ml). These results indicate that the antiplatelet activity of oxLDL may involve the following pathways. (1) oxLDL may initially induce conformational changes in platelet membranes, leading to inhibition of the activation of protein kinase C, followed by inhibition of P47 protein phosphorylation, and intracellular Ca2+ mobilization. (2) oxLDL also activated formation of cyclic AMP and cyclic AMP-induced VASP Ser157 phosphorylation, resulting in inhibition of the Na+/H+exchanger; this leads to reduced intracellular Ca2+ mobilization, and ultimately to inhibition of platelet aggregation. This study further provides new insights concerning the effects of low concentrations of oxLDL on platelet aggregation.
關聯:	J Biomed Sci.(13):333-343.
資料類型:	article
顯示於類別:	[藥理學科] 期刊論文

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