Plasma peroxidized low-density lipoprotein with hydroperoxidized cholesteryl linoleates estimated in patients with familial hypercholesterolemia.

A study was conducted to ascertain the presence of peroxidized low-density lipoprotein (LDL) in plasma and to determine the chemical structure of the peroxidized LDL so that the mechanism by which vascular complications develop may be elucidated in patients with familial hypercholesterolemia (FH). Family trees showing hypercholesterolemia and moderate grade thickness of the Achilles' tendon were confirmed in all patients. Cholesteryl ester, triglycerides (TG), free fatty acid (FFA), free cholesterol (FC), and phospholipids in normal LDL were stained on a thin-layer chromatography (TLC) plate, but from peroxidized LDL, spot X1 between TG and FFA, and spot X2 between FFA and FC were identified clearly except for the lipids recognized in normal LDL on the TLC plates. From intermediate-density lipoprotein (IDL), LDL1, and LDL2 of FH patients, spot X1 was clearly recognized. Hydroperoxidized cholesteryl linoleate (HPO-CL) was estimated and identified from Cu(2+)-treated standard CL, Cu(2+)-treated LDL and LDL obtained from FH patients by means of high-pressure liquid chromatography, mass spectrometry, nuclear magnetic resonance, positive reaction of p-methoxydiphenylpyrenyl-phosphine and various chemical reactions. The percentage of HPO-CL to total lipids in LDL was in the order of IDL < LDL1 < LDL2 in FH patients, and it was markedly higher in FH patients when compared to healthy persons. Spot X1 obtained from Cu(2+)-treated CL, from Cu(2+)-treated normal LDL and from LDL of FH patients was chemically identical, consisting of at least 4 kinds of HPO-CL isomer. LDL2-cholesterol levels were higher in FH patients than those of LDL1-cholesterol, whereas in healthy persons LDL1 cholesterol levels were higher compared to those of LDL2 cholesterol. The capacity of LDL2 for peroxidization by Cu2+ was greater than that of LDL1 in healthy persons. Biological functions, such as acceleration of platelet aggregation, great internalization into macrophages and injuries of the arterial endothelia, were reported for LDL with HPO-CL in our previous experiments. Thus, the existence of peroxidized LDL with HPO-CL may be one of the important risks for vascular complications in FH patients.