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Oxidized LDL-induced microvascular dysfunction. Dependence on oxidation procedure

L Liao, T Y Aw, P R Kvietys

    Arteriosclerosis, Thrombosis, and Vascular Biology
    |December 1, 1995
    PubMed
    Summary
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    Different forms of oxidized LDL were compared for their ability to promote inflammation. Copper-oxidized LDL (Cu-LDL) was most potent in inducing neutrophil-endothelial cell adhesion and vascular leakage.

    Area of Science:

    • Biochemistry
    • Vascular Biology
    • Immunology

    Background:

    • Human low-density lipoproteins (LDLs) oxidized by Cu2+ are known to promote leukocyte-endothelial cell adhesion (LECA) and albumin leakage.
    • Understanding the specific mechanisms and comparative effects of different LDL oxidation methods is crucial for cardiovascular research.

    Purpose of the Study:

    • To compare the pro-inflammatory potential of LDL oxidized via different methods: Cu2+ (Cu-LDL), phospholipase A2 plus lipoxygenase (PLA2-LDL), horseradish peroxidase plus H2O2 (HRP-LDL), and -OCl (-OCl-LDL).
    • To assess the in vitro induction of neutrophil-endothelial cell adhesion (NECA) and in vivo LECA and albumin leakage in rat mesenteric venules.

    Main Methods:

    • In vitro adhesion assays using neutrophils and endothelial cells incubated with various oxidized LDL forms.

    Related Experiment Videos

  • In vivo studies involving local intra-arterial infusion of oxidized LDL into rat mesenteric venules to assess leukocyte adherence, emigration, mast cell degranulation, and albumin leakage.

    • Main Results:

    • Only Cu-LDL elicited a dose-dependent NECA response in vitro. PLA2-LDL showed a significant increase at the highest concentration, while HRP-LDL and -OCl-LDL did not.
    • In vivo, Cu-LDL, PLA2-LDL, and -OCl-LDL significantly increased leukocyte adherence, emigration, mast cell degranulation, and albumin leakage.
    • The degree of lipid peroxidation correlated with NECA response magnitude, while protein oxidation levels did not.

    Conclusions:

    • Copper-mediated LDL oxidation is particularly effective at inducing NECA in vitro.
    • Various oxidized LDL species can trigger inflammatory responses in postcapillary venules, including leukocyte recruitment and vascular permeability.
    • The extent of lipid peroxidation, rather than protein oxidation, appears to be a key factor in the inflammatory potential of oxidized LDL.