Binding of oxidized low-density lipoprotein on circulating platelets is increased in patients with acute coronary syndromes and induces platelet adhesion to vascular wall in vivo--brief report.
OBJECTIVE
Hyperlipidemia is associated with platelet hyperactivity. In the present study, we evaluated the binding of oxidized low-density lipoprotein (oxLDL) on the surface of circulating platelets in patients with stable coronary artery disease and acute coronary syndromes and its possible association with platelet activation. Furthermore, the role of oxLDL binding on platelet adhesion to collagen and endothelial cells in vitro as well as after carotid ligation in mice was investigated.


RESULTS
Using flow cytometry, patients with acute coronary syndromes (n=174) showed significantly enhanced oxLDL binding compared with patients with stable coronary artery disease (n=182; P=0.007). Platelet-bound oxLDL positively correlated with the degree of platelet activation (expression of P-selectin and activated fibrinogen receptor; P<0.001 for both). Plasma oxLDL was increased in patients with acute coronary syndromes compared with stable angina pectoris patients. Preincubation of isolated platelets with oxLDL, but not with native LDL, resulted in enhanced platelet adhesion to collagen and activated endothelial cells under high shear stress in vitro, as well as after carotid ligation in C57BL/6J mice and apolipoprotein E(-/-) mice fed a high cholesterol diet.


CONCLUSIONS
Increased platelet-bound oxLDL in patients with acute coronary syndromes may play an important role in atherothrombosis, thus providing a potential future therapeutic target.
Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls-Universität Tübingen, Otfried-Müller Str.10, 72076 Tübingen, Germany.
Konstantinos
K
Stellos
Reinhard
R
Sauter
Manuela
M
Fahrleitner
Juliane
J
Grimm
Dimitrios
D
Stakos
Frederic
F
Emschermann
Victoria
V
Panagiota
Stephan
S
Gnerlich
Annegret
A
Perk
Tanja
T
Schönberger
Boris
B
Bigalke
Harald F
HF
Langer
Meinrad
M
Gawaz
D054058:Acute Coronary Syndrome / Q000097:blood*; D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology; D001792:Blood Platelets / Q000378:metabolism*; D042783:Endothelial Cells / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015539:Platelet Activation; D010973:Platelet Adhesiveness
D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein