Acidic pH increases the oxidation of LDL by macrophages

We have investigated the effect of pH on LDL oxidation by macrophages (in the presence of iron ions), using a modification of Hanks' balanced salt solution. Increasing the acidity of the medium greatly increased the oxidation of the LDL by the macrophages as measured by thiobarbituric acid-reactive substances or increased uptake and degradation by a second set of macrophages. The rate of oxidation of LDL by iron ions alone, measured in terms of conjugated dienes, was also increased greatly even at mildly acidic pH. It is quite possible that atherosclerotic lesions have an acidic extracellular pH, particularly in the vicinity of macrophages, and the observation that LDL oxidation by macrophages is increased at acidic pH may therefore help to explain why atherosclerotic lesions are apparently one of the very few sites in the body where LDL oxidation occurs.