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The Journal of Lipid Research, Vol. 39, 755-766, April 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages

Correspondence to: Germán Camejo.

Most models of lipoprotein oxidation by free radicals have excluded macromolecular plasma components from the system. This limits their biological significance because oxidation of lipoproteins appears to occur in the intima in the presence of a plasma ultrafiltrate. Hemin, a product of in vivo hemoglobin degradation, binds and oxidizes purified lipoproteins. However, it is not known whether this occurs in the presence of plasma components that may sequester hemin. We found that hemin in serum diluted to protein levels of the extracellular fluid (10–30%) binds to low and high density lipoproteins (LDL, HDL) with association constants in the nmol/L range. In the presence of H₂O₂, hemin oxidizes both lipoproteins in diluted serum with formation of conjugated dienes, thiobarbituric acid reacting substances, and F₂-isoprostanes. This appeared to be caused by the high affinity of hemin with LDL and by the Fe ³+ liberated that remains associated with the particles after hemin is degraded. Spectrophotometric and fluorescence experiments and electrophoresis of porphyrins complex with LDL indicated that the heme ring is buried in the lipoprotein surface-monolayer with the carboxylic groups in contact with positive regions of the protein and the solvent. Human macrophages associated and degraded 3- to 4-times more hemin-oxidized LDL in diluted serum than native LDL.

It is possible then that at sites of LDL accumulation in the extracellular intima, hemin and H₂O₂ production could cause oxidation with potential atherogenic consequences for cellular lipoprotein processing. This may occur even when other macromolecules of the extracellular fluid are present.—Camejo, G., C. Halberg, A. Menschik-Lundin, E. Hurt-Camejo, B. Rosengren, H. Olsson, G. I. Hansson, G-B. Forsberg, and B. Ylhen. Hemin binding and oxidation of lipoproteins in serum: mechanisms and effect on the interaction of LDL with human macrophages. J. Lipid Res. 1998. 39: 755–766.

Supplementary key words: lipoprotein oxidation, hemin binding, serum components, conjugated dienes, macrophages, lipoprotein degradation

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