OXIDIZED LDL-INDUCED MICROVASCULAR DYSFUNCTION - DEPENDENCE ON OXIDATION PROCEDURE

Human LDLs oxidized with Cu2+ are known to promote leukocyte-endotheli al cell adhesion (LECA) and albumin leakage in postcapillary venules. The objective of this study was to compare the ability of LDL oxidized with Cu2+ (Cu-LDL), phospholipase A(2) plus lipoxygenase (PLA(2)-LDL) , horseradish peroxidase plus H2O2 (HRP-LDL), or -OCl (-OCl-LDL) to pr omote (1)neutrophil- endothelial cell adhesion (NECA) in vitro and (2) LECA and albumin leakage in rat mesenteric venules. In vitro adhesion assays revealed that only Cu-LDL elicited a dose-dependent NECA respon se, whereas PLA(2)-LDL but not normal (N-LDL), HRP-LDL, or -OCl-LDL in creased NECA at the highest concentration studied (670 mu g/mL). The m agnitude of the NECA responses elicited by the different forms of oxid ized LDL was related to the degree of lipid peroxidation but unrelated to the level of protein oxidation. Local intra-arterial infusion of C u-LDL, PLA(2)-LDL, or -OCl-LDL but not N-LDL elicited significant incr eases in leukocyte adherence and emigration, mast cell degranulation, and albumin leakage in rat mesenteric venules. The LECA induced by all forms of oxidized LDL was not accompanied by significant alterations of venular shear rate.