LDL Oxidation Susceptibility and Its Relation To Antioxidants and Fatty Acids : A Clinical and Experimental Study

Abstract: Atherosclerosis is an arterial disease characterized by lipid deposits in the artery wall. These lipid deposits partly consist of oxidatively modified low density lipoprotein (LDL). Several lines of evidence indicate a role of oxidized LDL in atherogenesis. The susceptibility of human circulating LDL towards oxidation was therefore considered to be of interest.The LDL oxidation susceptibility was followed spectrophotometrically after addition of copper and was expressed as LDL lag time. We also investigated the plasma concentrations of oxidized cholesterol, lipophilic antioxidative vitamins and fatty acids to get a better understanding of the mechanisms governing LDL oxidation.We compared 50-54 year old men from Vilnius, Lithuania who have a four fold higher coronary heart disease (CHD) mortality compared to men from Link6ping, Sweden. Plasma or LDL cholesterol, blood pressure and smoking could not account for this difference. We found a significantly shorter Jag time in Vilnius men, higher serum concentrations of 7-ß hydroxycholesterol, lower concentrations of y-tocopherol, ß-carotene and lycopene and also higher amount of easily oxidized highly unsaturated fatty acids, such as eicosapentaenioc acid ( EPA). Important determinants of the LDL lag time were found to be EPA (negative), a-tocopherol (positive), but also LDL cholesterol and plasma triglyceride concentrations were associated with a shorter LDL lag time.The effect of ω-3 fatty acid compared to corn oil supplementation was investigated in patients with severe hypertriglyceridernia. Plasma triglyceride concentrations decreased by 48% in the ω-3 group. In both groups the LDL lag time shortened after 12 weeks of supplementation.In vitro addition of the antihypertensive drug captopril to LDL was investigated. Captopril prolonged the LDL lag time, decreased other oxidation products such as thiobarbituric acid reactive substances (TBARS) and lipid peroxides in a dose dependent manner.These studies show that the LDL oxidation susceptibility differs between two groups of healthy men from two populations with a marked difference in CHD mortality. Supplementation with ω-3 fatty acids shortened the LDL lag time. LDL oxidation susceptibility is related to low serum concentrations of lipophilic antioxidative vitamins and high content of long chain highly unsaturated fatty acids.