4-hydroxyphenylacetaldehyde and Hyperlipoproteinemia-Type-III

Very low density lipoproteins (VLDLs) from apolipoprotein (apo) E2/E2 subjects with type III hyperlipoproteinemia, VLDL remnants, and VLDL from apoE-knockout (EKO) mice are taken up poorly by macrophages. The present study examined whether VLDL modification by the reactive aldehyde p-hydroxyphenylacetaldehyde (pHA) enhances cholesteryl ester (CE) accumulation by J774A.1 macrophages. pHA is the major product derived from the oxidation of L-tyrosine by myeloperoxidase and is a component of human atherosclerotic lesions. Incubation of J774A.1 cells with native type III VLDL, their remnants, and EKO-VLDL increased cellular CE by only 3-, 5-, and 5-fold, respectively, compared with controls. In striking contrast, cells exposed to VLDL modified by purified pHA (pHA-VLDL) exhibited marked increases in cellular CE of 38-, 47-, and 35-fold, respectively (P95%, CE accumulation induced by copper-oxidized VLDL. These results demonstrate a novel mechanism for the conversion of type III VLDLs, their remnants, and EKO-VLDL into atherogenic particles and suggest that macrophage uptake of pHA-VLDL (1) requires catalytically active lipoprotein lipase, (2) involves acyl coenzyme A:cholesterol acyltransferase-mediated cholesterol esterification, and (3) involves pathways distinct from the SR-A.

Topics: Acetaldehyde; Animals; Apolipoproteins E; Arteriosclerosis; Cell Line; Cholesterol Esters; Esterification; Humans; Hyperlipoproteinemia Type III; Hypochlorous Acid; Interferon-gamma; Lipoprotein Lipase; Lipoproteins, VLDL; Macrophages; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidation-Reduction; Peroxidase; Phenol; Poly I; Receptors, Immunologic; Receptors, Lipoprotein; Receptors, Scavenger; Scavenger Receptors, Class A; Scavenger Receptors, Class B; Sterol O-Acyltransferase; Triglycerides; Tyrosine