Acidic pH enables caeruloplasmin to catalyse the modification of low-density lipoprotein

LDL oxidation within the arterial wall may contribute to the disease of atherosclerosis. There is some evidence that elevated plasma levels of copper are associated with an increased risk of coronary artery disease. We have investigated the conditions under which caeruloplasmin (the plasma copper carrier protein) can catalyse the macrophage-mediated modification of LDL. Low concentrations of CuSO4 (< 1 microM) could catalyse the macrophage-mediated modification of LDL. Native caeruloplasmin was unable to catalyse the modification of LDL at pH 7.4, but could do so after preincubation at acidic pH. After preincubation at acidic pH, concentrations of caeruloplasmin as low as 30 micrograms/ml (about one-tenth of the human plasma level) could catalyse significant LDL oxidation when added to macrophages. The activation of copper in caeruloplasmin in atherosclerotic lesions due to a localised acidic pH may help to explain why LDL oxidation occurs in these areas of the body.