Inhibitory mechanisms of low concentrations of oxidized low-density lipoprotein on platelet aggregation

Duen Suey Chou, Chih Hsiang Chan, George Hsiao, Ming Yi Shen, Yan Jyu Tsai, Tzeng-Fu Chen, Joen Rong Sheu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 μg/ml) inhibited platelet aggregation in human platelet-rich plasma stimulated by agonists. Moreover, oxLDL (40 and 80 μg/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 μg/ml) in phosphorus-32-labeled platelets. In addition, oxLDL (40 and 80 μg/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 μg/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.

Original languageEnglish
Pages (from-to)333-343
Number of pages11
JournalJournal of Biomedical Science
Volume13
Issue number3
DOIs
Publication statusPublished - May 2006

Fingerprint

Platelets
Platelet Aggregation
Agglomeration
Phosphorylation
Cyclic AMP
Blood Platelets
Protein Kinase C
oxidized low density lipoprotein
Chemical activation
Diphenylhexatriene
Membranes
Sodium-Hydrogen Antiporter
Platelet-Rich Plasma
Thrombin
Phosphorus
Proteins
Fluorescence
Plasmas

Keywords

  • Cyclic AMP
  • Na/H exchanger
  • oxLDL
  • Protein kinase C
  • Vasodilator-stimulated phosphoprotein

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Inhibitory mechanisms of low concentrations of oxidized low-density lipoprotein on platelet aggregation. / Chou, Duen Suey; Chan, Chih Hsiang; Hsiao, George; Shen, Ming Yi; Tsai, Yan Jyu; Chen, Tzeng-Fu; Sheu, Joen Rong.

In: Journal of Biomedical Science, Vol. 13, No. 3, 05.2006, p. 333-343.

Research output: Contribution to journalArticle

@article{8908c8d1402c42fb875eced96e56e03e,
title = "Inhibitory mechanisms of low concentrations of oxidized low-density lipoprotein on platelet aggregation",
abstract = "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 μg/ml) inhibited platelet aggregation in human platelet-rich plasma stimulated by agonists. Moreover, oxLDL (40 and 80 μg/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 μg/ml) in phosphorus-32-labeled platelets. In addition, oxLDL (40 and 80 μg/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 μg/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.",
keywords = "Cyclic AMP, Na/H exchanger, oxLDL, Protein kinase C, Vasodilator-stimulated phosphoprotein",
author = "Chou, {Duen Suey} and Chan, {Chih Hsiang} and George Hsiao and Shen, {Ming Yi} and Tsai, {Yan Jyu} and Tzeng-Fu Chen and Sheu, {Joen Rong}",
year = "2006",
month = "5",
doi = "10.1007/s11373-005-9042-x",
language = "English",
volume = "13",
pages = "333--343",
journal = "Journal of Biomedical Science",
issn = "1021-7770",
publisher = "BioMed Central",
number = "3",

}

TY - JOUR

T1 - Inhibitory mechanisms of low concentrations of oxidized low-density lipoprotein on platelet aggregation

AU - Chou, Duen Suey

AU - Chan, Chih Hsiang

AU - Hsiao, George

AU - Shen, Ming Yi

AU - Tsai, Yan Jyu

AU - Chen, Tzeng-Fu

AU - Sheu, Joen Rong

PY - 2006/5

Y1 - 2006/5

N2 - 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 μg/ml) inhibited platelet aggregation in human platelet-rich plasma stimulated by agonists. Moreover, oxLDL (40 and 80 μg/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 μg/ml) in phosphorus-32-labeled platelets. In addition, oxLDL (40 and 80 μg/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 μg/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.

AB - 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 μg/ml) inhibited platelet aggregation in human platelet-rich plasma stimulated by agonists. Moreover, oxLDL (40 and 80 μg/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 μg/ml) in phosphorus-32-labeled platelets. In addition, oxLDL (40 and 80 μg/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 μg/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.

KW - Cyclic AMP

KW - Na/H exchanger

KW - oxLDL

KW - Protein kinase C

KW - Vasodilator-stimulated phosphoprotein

UR - http://www.scopus.com/inward/record.url?scp=33646554518&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646554518&partnerID=8YFLogxK

U2 - 10.1007/s11373-005-9042-x

DO - 10.1007/s11373-005-9042-x

M3 - Article

VL - 13

SP - 333

EP - 343

JO - Journal of Biomedical Science

JF - Journal of Biomedical Science

SN - 1021-7770

IS - 3

ER -