Does an acidic pH explain why low density lipoprotein is oxidised in atherosclerotic lesions?
The oxidation of low density lipoprotein (LDL) within atherosclerotic lesions may be involved in atherogenesis. LDL oxidation by cells in the 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 LDL oxidation by copper ions is more complex, in that acidity slows down the initial oxidation, as measured by conjugated dienes, hydroperoxides and thiobarbituric acid-reactive substances, but can increase the later stages of LDL oxidation as measured by increased macrophage uptake. Extensive LDL oxidation by cells in atherosclerotic lesions probably 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 LDL 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 seen with concentrations of caeruloplasmin and transferrin below those present in plasma. By analogy to other inflammatory and ischaemic sites, atherosclerotic lesions may well have an acidic extracellular pH, particularly within clusters of macrophages where the oxidative stress may also be high. This localised acidic pH may help to explain why atherosclerotic lesions are one of the few sites in the body where extensive LDL oxidation occurs.
Leake
D S
DS
School of Animal and Microbial Sciences, University of Reading, Berkshire, UK.
D001161:Arteriosclerosis / Q000097:blood* / Q000150:complications; D002570:Ceruloplasmin / Q000378:metabolism; D002908:Chronic Disease; D003300:Copper / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry; D007674:Kidney Diseases / Q000150:complications; D008077:Lipoproteins, LDL / Q000097:blood*; D008247:Lysosomes / Q000378:metabolism; D010084:Oxidation-Reduction; D014168:Transferrin / Q000378:metabolism
D008077:Lipoproteins, LDL; D014168:Transferrin; C099252:oxidized low density lipoprotein; D003300:Copper; D007501:Iron; D002570:Ceruloplasmin; D003545:Cysteine