© 1995 American Heart Association, Inc.
Articles |
Mildly Oxidized LDL Induces Platelet Aggregation Through Activation of Phospholipase A2
From the Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, University of Munich, Germany.
Correspondence to Prof Dr W. Siess, Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Universität München, Pettenkoferstr 9, 80336 München, Germany.
Abstract Native LDL and LDL oxidized under various conditions
were compared in terms of their ability to activate
platelets. Native LDL did not induce platelet shape change or
aggregation, even at high concentrations (2 mg protein/mL). LDL was
mildly oxidized with either CuSO4 (mox-LDL) or
3-(N-morpholino)sydnonimine (SIN-1–LDL).
Analysis of mox-LDL and SIN-1–LDL showed a small
increase of dienes (E234nm from 0.28±0.04 to 0.55±0.09,
mean±SD) and thiobarbituric acid–reactive substance (from 0 to
10.6±1.5 nmol/mg, mean±SEM), no change in apo B electrophoretic
mobility, and a minor (12% to 30%) decrease in polyunsaturated fatty
acid content. Interestingly, this small oxidative modification of LDL
dramatically changed its effect on platelets. Irreversible
aggregation and secretion were induced by a threshold concentration of
0.4 mg protein/mL. In contrast, LDL thoroughly oxidized with
CuSO4 (ox-LDL) did not aggregate platelets. Although
mox-LDL was depleted in antioxidants (
- and
-tocopherol, - and ß-carotene, and other
carotenoids), incubation of mox-LDL with exogenous
-tocopherol did not reverse its ability to induce
platelet aggregation and secretion. Preincubation of platelets
with the cyclooxygenase inhibitor
aspirin or the phospholipase A2 inhibitors
trifluoperazine, quinacrine, 4-bromophenacyl bromide, and
propranolol completely prevented platelet aggregation
and secretion caused by mox-LDL or SIN-1–LDL. These results indicate
that mildly oxidized LDL activates platelets through a
phospholipase A2/cyclooxygenase–dependent pathway.
The complete inhibition of mox-LDL–induced platelet aggregation by
aspirin could contribute to its beneficial effect in
cardiovascular disease.
Key Words: platelet activation • LDL peroxidation • tocopherol • aspirin • SIN-1–LDL • LDL fatty acids
This article has been cited by other articles:
 |
|
 |
|
  E Matsuura and L. Lopez Autoimmune-mediated atherothrombosis Lupus, October 1, 2008; 17(10): 879 - 888. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Valiyaveettil, N. Kar, M. Z. Ashraf, T. V. Byzova, M. Febbraio, and E. A. Podrez Oxidized high-density lipoprotein inhibits platelet activation and aggregation via scavenger receptor BI Blood, February 15, 2008; 111(4): 1962 - 1971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J.A. Korporaal, M. Van Eck, J. Adelmeijer, M. Ijsseldijk, R. Out, T. Lisman, P. J. Lenting, T. J.C. Van Berkel, and J.-W. N. Akkerman Platelet Activation by Oxidized Low Density Lipoprotein Is Mediated by Cd36 and Scavenger Receptor-A Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2476 - 2483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Gleissner, N. Leitinger, and K. Ley Effects of Native and Modified Low-Density Lipoproteins on Monocyte Recruitment in Atherosclerosis Hypertension, August 1, 2007; 50(2): 276 - 283. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Calzada, L. Coulon, D. Halimi, E. Le Coquil, V. Pruneta-Deloche, P. Moulin, G. Ponsin, E. Vericel, and M. Lagarde In Vitro Glycoxidized Low-Density Lipoproteins and Low-Density Lipoproteins Isolated from Type 2 Diabetic Patients Activate Platelets via p38 Mitogen-Activated Protein Kinase J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1961 - 1964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Bruni, A. L. Pasqui, M. Pastorelli, G. Bova, M. Cercignani, A. Palazzuoli, T. Sawamura, A. Auteri, and L. Puccetti Different Effect of Statins on Platelet Oxidized-LDLReceptor (CD36 and LOX-1) Expressionin Hypercholesterolemic Subjects Clinical and Applied Thrombosis/Hemostasis, October 1, 2005; 11(4): 417 - 428. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Penz, A. J. Reininger, R. Brandl, P. Goyal, T. Rabie, I. Bernlochner, E. Rother, C. Goetz, B. Engelmann, P. A. Smethurst, et al. Human atheromatous plaques stimulate thrombus formation by activating platelet glycoprotein VI FASEB J, June 1, 2005; 19(8): 898 - 909. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J.A. Korporaal, G. Gorter, H. J.M. van Rijn, and J.-W. N. Akkerman Effect of Oxidation on the Platelet-Activating Properties of Low-Density Lipoprotein Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 867 - 872. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Coleman Jr, R. K. Polanowska-Grabowska, M. Marcinkiewicz, and A. R. L. Gear LDL oxidized by hypochlorous acid causes irreversible platelet aggregation when combined with low levels of ADP, thrombin, epinephrine, or macrophage-derived chemokine (CCL22) Blood, July 15, 2004; 104(2): 380 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhang, D. L. Baker, S. Yasuda, N. Makarova, L. Balazs, L. R. Johnson, G. K. Marathe, T. M. McIntyre, Y. Xu, G. D. Prestwich, et al. Lysophosphatidic Acid Induces Neointima Formation Through PPAR{gamma} Activation J. Exp. Med., March 15, 2004; 199(6): 763 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A. M. Relou, G. Gorter, I. A. Ferreira, H. J. M. van Rijn, and J.-W. N. Akkerman Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) Inhibits Low Density Lipoprotein-induced Signaling in Platelets J. Biol. Chem., August 29, 2003; 278(35): 32638 - 32644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Rother, R. Brandl, D. L. Baker, P. Goyal, H. Gebhard, G. Tigyi, and W. Siess Subtype-Selective Antagonists of Lysophosphatidic Acid Receptors Inhibit Platelet Activation Triggered by the Lipid Core of Atherosclerotic Plaques Circulation, August 12, 2003; 108(6): 741 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Ferretti, R. A. Rabini, T. Bacchetti, A. Vignini, E. Salvolini, F. Ravaglia, G. Curatola, and L. Mazzanti Glycated Low Density Lipoproteins Modify Platelet Properties: A Compositional and Functional Study J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2180 - 2184. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kobayashi, E. Matsuura, Q. Liu, J.-i. Furukawa, K. Kaihara, J. Inagaki, T. Atsumi, N. Sakairi, T. Yasuda, D. R. Voelker, et al. A specific ligand for {beta}2-glycoprotein I mediates autoantibody-dependent uptake of oxidized low density lipoprotein by macrophages J. Lipid Res., May 1, 2001; 42(5): 697 - 709. [Abstract] [Full Text]
|
|
|
|
|
|
I. Volf, E. Bielek, T. Moeslinger, F. Koller, and E. Koller Modification of Protein Moiety of Human Low Density Lipoprotein by Hypochlorite Generates Strong Platelet Agonist Arterioscler Thromb Vasc Biol, August 1, 2000; 20(8): 2011 - 2018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Parthasarathy, N. Santanam, S. Ramachandran, and O. Meilhac Oxidants and antioxidants in atherogenesis: an appraisal J. Lipid Res., December 1, 1999; 40(12): 2143 - 2157. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Koba, R. Pakala, T. Watanabe, T. Katagiri, and C. R. Benedict Vascular smooth muscle proliferation: Synergistic interaction between serotonin and low density lipoproteins J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1644 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Essler, M. Retzer, M. Bauer, J. W. Heemskerk, M. Aepfelbacher, and W. Siess Mildly Oxidized Low Density Lipoprotein Induces Contraction of Human Endothelial Cells through Activation of Rho/Rho Kinase and Inhibition of Myosin Light Chain Phosphatase J. Biol. Chem., October 22, 1999; 274(43): 30361 - 30364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Siess, K. J. Zangl, M. Essler, M. Bauer, R. Brandl, C. Corrinth, R. Bittman, G. Tigyi, and M. Aepfelbacher Lysophosphatidic acid mediates the rapid activation of platelets and endothelial cells by mildly oxidized low density lipoprotein and accumulates in human atherosclerotic lesions PNAS, June 8, 1999; 96(12): 6931 - 6936. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Honda, N. Leitinger, M. Frankel, J. I. Goldhaber, R. Natarajan, J. L. Nadler, J. N. Weiss, and J. A. Berliner Induction of Monocyte Binding to Endothelial Cells by MM-LDL : Role of Lipoxygenase Metabolites Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 680 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Hackeng, M. Huigsloot, M. W. Pladet, H. K. Nieuwenhuis, H. J. M. van Rijn, and J.-W. N. Akkerman Low-Density Lipoprotein Enhances Platelet Secretion Via Integrin-{alpha}IIbß3–Mediated Signaling Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 239 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Knight, M. Panesar, C. Wright, D. Clarke, P. S. Butowski, D. Patel, A. Patrineli, K. Fox, and A. H. Goodall Altered Platelet Function Detected by Flow Cytometry : Effects of Coronary Artery Disease and Age Arterioscler Thromb Vasc Biol, October 1, 1997; 17(10): 2044 - 2053. [Abstract] [Full Text]
|
|
|
|
|
|
J.-R. Nofer, M. Tepel, B. Kehrel, S. Wierwille, M. Walter, U. Seedorf, W. Zidek, and G. Assmann Low-Density Lipoproteins Inhibit the Na+/H+ Antiport in Human Platelets: A Novel Mechanism Enhancing Platelet Activity in Hypercholesterolemia Circulation, March 18, 1997; 95(6): 1370 - 1377. [Abstract] [Full Text]
|
|
|
|
|
|
M. W. Anthonsen, A. Solhaug, and B. Johansen Functional Coupling between Secretory and Cytosolic Phospholipase A2 Modulates Tumor Necrosis Factor-alpha - and Interleukin-1beta -induced NF-kappa B Activation J. Biol. Chem., August 3, 2001; 276(32): 30527 - 30536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Maschberger, M. Bauer, J. Baumann-Siemons, K. J. Zangl, E. V. Negrescu, A. J. Reininger, and W. Siess Mildly Oxidized Low Density Lipoprotein Rapidly Stimulates via Activation of the Lysophosphatidic Acid Receptor Src Family and Syk Tyrosine Kinases and Ca2+ Influx in Human Platelets J. Biol. Chem., June 16, 2000; 275(25): 19159 - 19166. [Abstract] [Full Text] [PDF]
|
|