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Updated: Jul 12, 2026

Alternative Methods for the Detection of Superoxide Anion Generation in Platelets
Published on: March 29, 2024
Platelet activation by oxidized low density lipoprotein is mediated by CD36 and scavenger receptor-A
Suzanne J A Korporaal1, Miranda Van Eck, Jelle Adelmeijer
1Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, and Institute of Biomembranes, Utrecht University, The Netherlands.
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(MAPK) and by oxidized LDL (oxLDL) through lysophosphatidic acid (LPA) signaling to Rho A and Ca2+. Here we report a new mechanism for platelet activation by oxLDL.
Methods And Results:
Oxidation of nLDL increases p38(MAPK) 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(MAPK) activation by oxLDL but combined blockade inhibits p38(MAPK) by >40% and platelet adhesion to fibrinogen under flow by >60%. Mouse platelets deficient in either CD36 or SR-A show normal p38(MAPK) activation by oxLDL but combined deficiency of CD36 and SR-A disrupts oxLDL-induced activation of p38(MAPK) 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.
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