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(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.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 27 Issue 11 Pg. 2476-83 (Nov 2007) ISSN: 1524-4636 [Electronic] United States
• PMID: 17761940 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD36 Antigens
• Lipoproteins, LDL
• Scavenger Receptors, Class A
• oxidized low density lipoprotein
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Blood Platelets
• CD36 Antigens (physiology)
• Humans
• Lipoproteins, LDL (physiology)
• Mice
• Mice, Knockout
• Platelet Activation (physiology)
• Scavenger Receptors, Class A (physiology)
• Signal Transduction (physiology)
• p38 Mitogen-Activated Protein Kinases (metabolism)