title: Highly electronegative LDL from patients with ST-elevation myocardial infarction triggers platelet activation and aggregation.
abstract: Platelet activation and aggregation underlie acute thrombosis that leads to ST-elevation myocardial infarction (STEMI). L5-highly electronegative low-density lipoprotein (LDL)-is significantly elevated in patients with STEMI. Thus, we examined the role of L5 in thrombogenesis. Plasma LDL from patients with STEMI (n = 30) was chromatographically resolved into 5 subfractions (L1-L5) with increasing electronegativity. In vitro, L5 enhanced adenosine diphosphate-stimulated platelet aggregation twofold more than did L1 and induced platelet-endothelial cell (EC) adhesion. L5 also increased P-selectin expression and glycoprotein (GP)IIb/IIIa activation and decreased cyclic adenosine monophosphate levels (n = 6, P < .01) in platelets. In vivo, injection of L5 (5 mg/kg) into C57BL/6 mice twice weekly for 6 weeks shortened tail bleeding time by 43% (n = 3; P < .01 vs L1-injected mice) and increased P-selectin expression and GPIIb/IIIa activation in platelets. Pharmacologic blockade experiments revealed that L5 signals through platelet-activating factor receptor and lectin-like oxidized LDL receptor-1 to attenuate Akt activation and trigger granule release and GPIIb/IIIa activation via protein kinase C-α. L5 but not L1 induced tissue factor and P-selectin expression in human aortic ECs (P < .01), thereby triggering platelet activation and aggregation with activated ECs. These findings indicate that elevated plasma levels of L5 may promote thrombosis that leads to STEMI.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
authors.forename: Hua-Chen
authors.initials: HC
authors.lastname: Chan
authors.forename: Liang-Yin
authors.initials: LY
authors.lastname: Ke
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chu
authors.forename: An-Sheng
authors.initials: AS
authors.lastname: Lee
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Shen
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Cruz
authors.forename: Jing-Fang
authors.initials: JF
authors.lastname: Hsu
authors.forename: Kai-Hung
authors.initials: KH
authors.lastname: Cheng
authors.forename: Hsiu-Chuan Bonnie
authors.initials: HC
authors.lastname: Chan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lu
authors.forename: Wen-Ter
authors.initials: WT
authors.lastname: Lai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.forename: Sheng-Hsiung
authors.initials: SH
authors.lastname: Sheu
authors.forename: Jeng-Hsien
authors.initials: JH
authors.lastname: Yen
authors.forename: Chu-Huang
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D000242:Cyclic AMP / Q000097:blood; D004563:Electrochemistry; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000097:blood* / Q000209:etiology; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D051571:Protein Kinase C-alpha / Q000097:blood; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000097:blood; D051127:Scavenger Receptors, Class E / Q000037:antagonists & inhibitors / Q000097:blood / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D013927:Thrombosis / Q000097:blood / Q000209:etiology
chemical_list: D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; C495138:Olr1 protein, mouse; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D051127:Scavenger Receptors, Class E; C039351:platelet activating factor receptor; D000242:Cyclic AMP; C496628:PRKCA protein, human; D051571:Protein Kinase C-alpha
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