on August 30, 2007
Published online before print August 30, 2007, doi: 10.1161/ATVBAHA.107.150698
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on July 31, 2006
Accepted on August 2, 2007
Platelet Activation by Oxidized Low Density Lipoprotein Is Mediated by Cd36 and Scavenger Receptor-A
Suzanne J.A. Korporaal ;
From the Department of Clinical Chemistry and Haematology (S.J.A.K., J.A., M.I., T.L., P.J.L., J.-W.N.A.), University Medical Center Utrecht, and Institute of Biomembranes, Utrecht University, the Netherlands; and the Division of Biopharmaceutics (M.V.E., R.O., T.J.C.V.B.), Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, the Netherlands.
* To whom correspondence should be addressed. E-mail: j.w.n.akkerman{at}umcutrecht.nl.
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 p38MAPK 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 p38MAPK 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 p38MAPK activation by oxLDL but combined blockade inhibits p38MAPK by >40% and platelet adhesion to fibrinogen under flow by >60%. Mouse platelets deficient in either CD36 or SR-A show normal p38MAPK activation by oxLDL but combined deficiency of CD36 and SR-A disrupts oxLDL-induced activation of p38MAPK 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.
Key words: platelets • LDL • oxidized LDL • CD36 • scavenger receptor-A
This article has been cited by other articles:
 |
|
 |
|
  K. Chen, M. Febbraio, W. Li, and R. L. Silverstein A Specific CD36-Dependent Signaling Pathway Is Required for Platelet Activation by Oxidized Low-Density Lipoprotein Circ. Res., June 20, 2008; 102(12): 1512 - 1519. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Siegel-Axel, K. Daub, P. Seizer, S. Lindemann, and M. Gawaz Platelet lipoprotein interplay: trigger of foam cell formation and driver of atherosclerosis Cardiovasc Res, April 1, 2008; 78(1): 8 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Collot-Teixeira, F. Delorenzo, and J. L. McGregor Scavenger Receptor A and CD36 Are Implicated in Mediating Platelet Activation Induced by Oxidized Low- Density Lipoproteins Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2491 - 2492. [Full Text] [PDF]
|
|