The oxidative conversion of LDL into an atherogenic form is considered a pivotal event in the development of cardiovascular disease. Recent studies have identified reactive nitrogen species generated by monocytes by way of the myeloperoxidase-hydrogen peroxide-nitrite (MPO-H(2)O(2)-NO(2)(-)) system as a novel mechanism for converting LDL into a high-uptake form (NO(2)-LDL) for macrophages. We n...

We have examined whether oxidized low-density lipoprotein (ox-LDL) affects the function of tissue-factor-pathway inhibitor (TFPI), an anti-coagulant regulator in the extrinsic pathway of coagulation, in cultured human umbilical vein endothelial cells (HUVEC). Treatment of culture medium of HUVEC with ox-LDL, but not with native or acetylated LDLs, drastically decreased the reactivity of TFPI to...

Seven monoclonal antibodies against human low density lipoprotein (LDL) have been characterized as to their specificity and ability to interfere with the LDL pathway in cultured human fibroblasts. The immunoreactivity with LDL of two of the antibodies (2D8 and 4G3) was particularly sensitive to modification of lysine and arginine residues in LDL. Cotitration experiments indicated that the antib...

Oxidative modification of low density lipoproteins (LDL) has been shown to cause accelerated degradation of LDL via the scavenger receptor pathway in cultured macrophages, and it has been proposed that this process might lead to cholesterol accumulation in macrophages in the arterial wall in vivo. However, oxidation of LDL is accompanied by a substantial reduction in LDL total cholesterol conte...

C-reactive protein (CRP), an acute-phase reactant, is present in atherosclerotic human arterial intima in association with lipids. In the present work we studied interactions between CRP and LDL on microtitre wells, where either CRP or LDL was immobilized. LDL was modified by vortex-mixing, oxidation, or by lipolysis with phospholipase A(2) or with sphingomyelinase or a combination of trypsin a...

Oxidation of LDL is thought to be involved in both initiating and sustaining atherogenesis through the formation of proinflammatory lipids and the covalent modification of LDL particles. Platelet-activating factor (PAF; 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent phospholipid mediator involved in inflammation. Upon oxidation of LDL, oxidized phospholipids with PAF-like structure...

In peripheral blood, native low-density lipoprotein (LDL) is a major carrier of acetylhydrolase, the enzyme that hydrolyzes the sn-2 acetate of PAF-acether, converting it to lyso PAF-acether. By controlling the level of PAF-acether, the acetylhydrolase may regulate the biologic effects of this potent inflammatory and thrombotic mediator. The biologic oxidation of LDL appears to underlie its ath...

Macrophage uptake of modified forms ofLDL leads to cellular cholesterol accumulation. Upon incubation of LDL with phospholipase D (PLase D), a timeand enzyme dose-dependent production of phosphatidic acid (PA), paralleled by a rapid reduction in LDL phosphatidyl choline content (up to 65% within 15 min of incubation) was noted. No lipid peroxidation could be found in PLase D-modified LDL. Upon ...

Coronary artery calcification (CAC) reflects the anatomic presence of coronary atherosclerosis and the relative burden of coronary artery disease (CAD). Higher levels of CAC are seen in the presence of CAD risk factors, older age, and chronic kidney disease. The lipid profile (primarily low HDL cholesterol, elevated triglycerides, elevated LDL cholesterol, and elevated total cholesterol) are im...

Hypercholesterolemia, cigarette smoking, hypertension, and obesity are known contributing risk factors for the development of atherosclerotic coronary artery disease (CAD). However, they account for only half of all cases of CAD, and the complete pathologic process underlying atherosclerosis remains unknown. Growing evidence suggests that oxidative modification of low-density lipoprotein (LDL) ...