Platelet activation by oxidized low density lipoprotein is mediated by Cd36 and scavenger receptor-A

Suzanne J A Korporaal; Miranda Van Eck; Jelle Adelmeijer; Martin Ijsseldijk; Ruud Out; Ton Lisman; Peter J. Lenting; Theo J C Van Berkel; Jan Willem N Akkerman

doi:10.1161/ATVBAHA.107.150698

Platelet activation by oxidized low density lipoprotein is mediated by Cd36 and scavenger receptor-A

Suzanne J A Korporaal, Miranda Van Eck, Jelle Adelmeijer, Martin Ijsseldijk, Ruud Out, Ton Lisman, Peter J. Lenting, Theo J C Van Berkel, Jan Willem N Akkerman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

43 Citations (Scopus)

Abstract

OBJECTIVE - The interaction of platelets with low density lipoprotein (LDL) contributes to the development of cardiovascular disease. Platelets are activated by native LDL (nLDL) through apoE Receptor 2′ (apoER2′)-mediated signaling to p38 and by oxidized LDL (oxLDL) through lysophosphatidic acid (LPA) signaling to Rho A and Ca. Here we report a new mechanism for platelet activation by oxLDL. METHODS AND RESULTS - Oxidation of nLDL increases p38 activation through a mechanism that is (1) independent of LPA, and (2) unlike nLDL-signaling not desensitized by prolonged platelet-LDL contact or inhibited by receptor-associated protein or chondroitinase ABC. Antibodies against scavenger receptors CD36 and SR-A alone fail to block p38 activation by oxLDL but combined blockade inhibits p38 by >40% and platelet adhesion to fibrinogen under flow by >60%. Mouse platelets deficient in either CD36 or SR-A show normal p38 activation by oxLDL but combined deficiency of CD36 and SR-A disrupts oxLDL-induced activation of p38 by >70%. CONCLUSION - These findings reveal a novel platelet-activating pathway stimulated by oxLDL that is initiated by the combined action of CD36 and SR-A.

Original language	English
Pages (from-to)	2476-2483
Number of pages	8
Journal	Arteriosclerosis, Thrombosis and Vascular Biology
Volume	27
Issue number	11
DOIs	https://doi.org/10.1161/ATVBAHA.107.150698
Publication status	Published - 1 Nov 2007

Keywords

CD36
LDL
Oxidized LDL
Platelets
Scavenger receptor-A

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10.1161/ATVBAHA.107.150698

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title = "Platelet activation by oxidized low density lipoprotein is mediated by Cd36 and scavenger receptor-A",

abstract = "OBJECTIVE - The interaction of platelets with low density lipoprotein (LDL) contributes to the development of cardiovascular disease. Platelets are activated by native LDL (nLDL) through apoE Receptor 2′ (apoER2′)-mediated signaling to p38 and by oxidized LDL (oxLDL) through lysophosphatidic acid (LPA) signaling to Rho A and Ca. Here we report a new mechanism for platelet activation by oxLDL. METHODS AND RESULTS - Oxidation of nLDL increases p38 activation through a mechanism that is (1) independent of LPA, and (2) unlike nLDL-signaling not desensitized by prolonged platelet-LDL contact or inhibited by receptor-associated protein or chondroitinase ABC. Antibodies against scavenger receptors CD36 and SR-A alone fail to block p38 activation by oxLDL but combined blockade inhibits p38 by >40% and platelet adhesion to fibrinogen under flow by >60%. Mouse platelets deficient in either CD36 or SR-A show normal p38 activation by oxLDL but combined deficiency of CD36 and SR-A disrupts oxLDL-induced activation of p38 by >70%. CONCLUSION - These findings reveal a novel platelet-activating pathway stimulated by oxLDL that is initiated by the combined action of CD36 and SR-A.",

keywords = "CD36, LDL, Oxidized LDL, Platelets, Scavenger receptor-A",

author = "Korporaal, {Suzanne J A} and {Van Eck}, Miranda and Jelle Adelmeijer and Martin Ijsseldijk and Ruud Out and Ton Lisman and Lenting, {Peter J.} and {Van Berkel}, {Theo J C} and Akkerman, {Jan Willem N}",

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doi = "10.1161/ATVBAHA.107.150698",

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T1 - Platelet activation by oxidized low density lipoprotein is mediated by Cd36 and scavenger receptor-A

AU - Korporaal, Suzanne J A

AU - Van Eck, Miranda

AU - Adelmeijer, Jelle

AU - Ijsseldijk, Martin

AU - Out, Ruud

AU - Lisman, Ton

AU - Lenting, Peter J.

AU - Van Berkel, Theo J C

AU - Akkerman, Jan Willem N

PY - 2007/11/1

Y1 - 2007/11/1

N2 - OBJECTIVE - The interaction of platelets with low density lipoprotein (LDL) contributes to the development of cardiovascular disease. Platelets are activated by native LDL (nLDL) through apoE Receptor 2′ (apoER2′)-mediated signaling to p38 and by oxidized LDL (oxLDL) through lysophosphatidic acid (LPA) signaling to Rho A and Ca. Here we report a new mechanism for platelet activation by oxLDL. METHODS AND RESULTS - Oxidation of nLDL increases p38 activation through a mechanism that is (1) independent of LPA, and (2) unlike nLDL-signaling not desensitized by prolonged platelet-LDL contact or inhibited by receptor-associated protein or chondroitinase ABC. Antibodies against scavenger receptors CD36 and SR-A alone fail to block p38 activation by oxLDL but combined blockade inhibits p38 by >40% and platelet adhesion to fibrinogen under flow by >60%. Mouse platelets deficient in either CD36 or SR-A show normal p38 activation by oxLDL but combined deficiency of CD36 and SR-A disrupts oxLDL-induced activation of p38 by >70%. CONCLUSION - These findings reveal a novel platelet-activating pathway stimulated by oxLDL that is initiated by the combined action of CD36 and SR-A.

AB - OBJECTIVE - The interaction of platelets with low density lipoprotein (LDL) contributes to the development of cardiovascular disease. Platelets are activated by native LDL (nLDL) through apoE Receptor 2′ (apoER2′)-mediated signaling to p38 and by oxidized LDL (oxLDL) through lysophosphatidic acid (LPA) signaling to Rho A and Ca. Here we report a new mechanism for platelet activation by oxLDL. METHODS AND RESULTS - Oxidation of nLDL increases p38 activation through a mechanism that is (1) independent of LPA, and (2) unlike nLDL-signaling not desensitized by prolonged platelet-LDL contact or inhibited by receptor-associated protein or chondroitinase ABC. Antibodies against scavenger receptors CD36 and SR-A alone fail to block p38 activation by oxLDL but combined blockade inhibits p38 by >40% and platelet adhesion to fibrinogen under flow by >60%. Mouse platelets deficient in either CD36 or SR-A show normal p38 activation by oxLDL but combined deficiency of CD36 and SR-A disrupts oxLDL-induced activation of p38 by >70%. CONCLUSION - These findings reveal a novel platelet-activating pathway stimulated by oxLDL that is initiated by the combined action of CD36 and SR-A.

KW - CD36

KW - LDL

KW - Oxidized LDL

KW - Platelets

KW - Scavenger receptor-A

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JO - Arteriosclerosis, Thrombosis and Vascular Biology

JF - Arteriosclerosis, Thrombosis and Vascular Biology

IS - 11

ER -

Platelet activation by oxidized low density lipoprotein is mediated by Cd36 and scavenger receptor-A

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