Oxidized LDL–Induced Microvascular Dysfunction

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Abstract
Abstract Human LDLs oxidized with Cu 2+ are known to promote leukocyte–endothelial cell adhesion (LECA) and albumin leakage in postcapillary venules. The objective of this study was to compare the ability of LDL oxidized with Cu 2+ (Cu-LDL), phospholipase A 2 plus lipoxygenase (PLA 2 -LDL), horseradish peroxidase plus H 2 O 2 (HRP-LDL), or −OCl (−OCl-LDL) to promote (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 response, whereas PLA 2 -LDL but not normal (N-LDL), HRP-LDL, or −OCl-LDL increased NECA at the highest concentration studied (670 μg/mL). The magnitude of the NECA responses elicited by the different forms of oxidized LDL was related to the degree of lipid peroxidation but unrelated to the level of protein oxidation. Local intra-arterial infusion of Cu-LDL, PLA 2 -LDL, or −OCl-LDL but not N-LDL elicited significant increases 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.