Abstract
Background:
Oxidation of LDL produces a series of biologically active, oxidized lipids. Among them, isoprostanes, and in particular iPF(2alpha)-III, seem to be crucial in mediating some of the key cellular events seen in myocardial ischemia-reperfusion injury.
Methods and results:
Minimally modified LDL (MM-LDL) triggers a dose-dependent, very rapid neutrophil adhesion to human fibrinogen. Rapid adhesion triggering correlates with degree of LDL oxidation and accumulation of isoprostanes. Isoprostanes accumulated in MM-LDL are major determinants of the proadhesive effect of oxidized LDL, as shown by experiments of receptor functional deletion. Moreover, evidence is provided of expression on human neutrophils of a biological active isoprostane receptor distinct from the classical thromboxane A2 receptor.
Conclusions:
These data suggest that isoprostanes are major contributors to the proadhesive effect induced by MM-LDL on neutrophils and provide additional evidence for the involvement of isoprostanes in the pathogenesis of myocardial ischemia/reperfusion injury.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
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Blood Platelets / cytology
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Blood Platelets / physiology
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Bridged Bicyclo Compounds, Heterocyclic
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CD18 Antigens / metabolism*
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Cell Adhesion / drug effects
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Cell Adhesion / immunology
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F2-Isoprostanes / metabolism*
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Fatty Acids, Unsaturated
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Fibrinogen / metabolism
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GTP-Binding Protein alpha Subunits, Gi-Go / drug effects
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GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
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Humans
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Hydrazines / pharmacology
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Intercellular Adhesion Molecule-1 / metabolism
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Lipoproteins, LDL / chemistry
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Lipoproteins, LDL / pharmacology*
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Lipoproteins, LDL / radiation effects
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Neutrophils / cytology
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Neutrophils / drug effects
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Neutrophils / physiology*
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Pertussis Toxin / pharmacology
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Receptors, Thromboxane / agonists
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Receptors, Thromboxane / antagonists & inhibitors
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Ultraviolet Rays
Substances
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Bridged Bicyclo Compounds, Heterocyclic
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CD18 Antigens
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F2-Isoprostanes
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Fatty Acids, Unsaturated
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Hydrazines
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Lipoproteins, LDL
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Receptors, Thromboxane
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oxidized low density lipoprotein
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Intercellular Adhesion Molecule-1
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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SQ 29548
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Fibrinogen
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Pertussis Toxin
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GTP-Binding Protein alpha Subunits, Gi-Go