DOES AN ACIDIC PH EXPLAIN WHY LOW-DENSITY-LIPOPROTEIN IS OXIDIZED IN ATHEROSCLEROTIC LESIONS

The oxidation of low density lipoprotein (LDL) within atherosclerotic lesions may be involved in atherogenesis. LDL oxidation by cells in th e presence of iron is faster at acidic pH. In addition, LDL oxidation by iron alone or iron-cysteine in the absence of cells is much faster at acidic pH, even at mildly acidic pH (pH 6.5). The effect of pH on L DL oxidation by copper ions is more complex, in that acidity slows dow n the initial oxidation, as measured by conjugated dienes, hydroperoxi des and thiobarbituric acid-reactive substances, but can increase the later stages of LDL oxidation as measured by increased macrophage upta ke. Extensive LDL oxidation by cells in atherosclerotic lesions probab ly requires a source of iron or copper as catalysts for the oxidation. Iron in plasma is carried by the protein transferrin. Lowering the pH releases some of the iron from transferrin so that it can catalyse LD L oxidation. Copper is carried in plasma on caeruloplasmin and becomes more effective in catalysing LDL oxidation when the caeruloplasmin is preincubated at acidic pH, or even at pH 7.0. These effects can be se en with concentrations of caeruloplasmin and transferrin below those p resent in plasma. By analogy to other inflammatory and ischaemic sites , atherosclerotic lesions may well have an acidic extracellular pH, pa rticularly within clusters of macrophages where the oxidative stress m ay also be high. This localised acidic pH may help to explain why athe rosclerotic lesions are one of the few sites in the body where extensi ve LDL oxidation occurs. (C) 1997 Elsevier Science Ireland Ltd.