Lipoprotein lipase (LPL) stimulates the uptake of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) in different cell types, including macrophages, through bridging of LPL between lipoproteins and extracellular heparan sulphate proteoglycans (HSPG). Because macrophages produce LPL and because modified lipoproteins are present in the arterial wall in vivo, we wondered whether...

OBJECTIVE To study the association of PAF-acetyl hydrolase (PAFAH) activity with inflammation, oxidative stress, and atherosclerosis in hypercholesterolemic swine. METHODS AND RESULTS Cholesterol-rich diet feeding of miniature pigs was associated with an increase in PAFAH activity and an increase of the PAFAH to PON1 ratio. PLA2G7 RNA (coding for PAFAH) expression was increased in blood monoc...

Mounting evidence supports current theories linking lipoprotein oxidation to atherosclerosis. We sought the cellular biochemical mechanism by which oxidized LDL inflicts cell injury. Inhibitors of candidate pathways of cell death were used to treat human fibroblast target cells exposed to oxidized LDL.. Ebselen, which degrades lipid hydroperoxides, inhibited oxidized LDL toxicity, consistent wi...

Tissue factor, which is expressed in vascular lesions, increases thrombin production, blood coagulation, and smooth muscle cell proliferation. We demonstrate that oxidized low-density lipoprotein (LDL) induces surface tissue factor pathway activity (ie, activity of the tissue factor: factor VIIa complex) on human and rat smooth muscle cells. Tissue factor messenger RNA (mRNA) was induced by oxi...

The monoclonal antibody 4E6-based ELISA was used to quantify levels of oxidized LDL in plasma of 65 control subjects, 47 patients transplanted for dilated cardiomyopathy (DCM), and 60 patients transplanted for coronary artery disease (CAD). Levels of oxidized LDL were 0.68+/-0.039 mg/dL (mean+/-SEM), 1.27+/-0.14 mg/dL (P<.001 versus control), and 1.73+/-0.13 mg/dL (P<.001 versus control and <0....

BACKGROUND & OBJECTIVES Paraoxonase (PON) is an HDL associated ester hydrolase with an ability to retard LDL oxidation in vitro by preventing lipid peroxide generation. The population variability in enzyme activity is attributed to polymorphisms in paraoxonase gene. For example, polymorphism at codon 192 and 55 of the paraoxonase gene has been reported to be associated with coronary heart disea...

An inactivated form of 1-antitrypsin (AT) and LDL coelutes in gel permeation chromatography. To characterize and to quantify the amount of this fraction of AT, a monoclonal antibody was established against chloramine T–oxidized AT and named OxAT-4. OxAT-4 recognized the oxidatively modified AT, including hexylaldehydeor 4-hydroxy-2-nonenal–modified AT, but neither normal active AT nor trypsin/A...

The oxidative modification of low-density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis, although little is known as yet about the precise mechanism of oxidation in vivo. The studies presented here demonstrate that, in the absence of cells or transition metals, oxidized LDL can modify native LDL through co-incubation in vitro such as to increase its net negative c...

BACKGROUND The association between oxidative modifications of LDL and coronary artery disease (CAD) is suspected but not established. Therefore, the association between plasma levels of oxidized LDL and malondialdehyde (MDA)-modified LDL and acute coronary syndromes and stable CAD was investigated. METHODS AND RESULTS The study population contained 63 patients with acute coronary syndromes (4...