Atherosclerosis and sensitive determination of oxidized LDL using monoclonal antibody

Abstract

Oxidized low-density lipoprotein (OxLDL) is thought to be involved in atherosclerotic lesion formation. We established a monoclonal antibody, DLH3, that recognizes oxidized phosphatidylcholine (OxPC) formed in OxLDL. A sensitive method for detecting OxLDL was enabled by a sandwich ELISA procedure utilizing DLH3 together with an anti-apoB antibody. Using the method, we demonstrated the presence of OxLDL in human circulating plasma for the first time, and the plasma OxLDL level in healthy subjects was estimated to be about 0.1 ng/μg LDL protein. OxLDL levels in patients with acute myocardial infarction are more than 3 times higher than in controls. Thus the plasma OxLDL level could be a good marker for cardiovascular disease. There are multiple metabolic enzymes for OxPC in plasma. We demonstrated that lecithin: cholesterol acyltransferase (LCAT) is capable of metabolizing OxPC molecules in OxLDL, and that the plasma OxLDL level in patients with familial LCAT deficiency was about 3.5 times higher than in controls. OxLDL in vivo is likely to be metabolized by enzymatic activities in plasma, the reticuloendothelial system including Kupffer cells, and immunological responses. The OxLDL levels determined by this analytical procedure would reflect the physiologic balance between oxidative modification of LDL and metabolic clearance of OxLDL. © 2002 The Pharmaceutical Society of Japan.