Oxidized LDL induces procoagulant profiles by increasing lysophosphatidylcholine levels, lysophosphatidylethanolamine levels, and Lp-PLA2 activity in borderline hypercholesterolemia

The increased risk of cardiovascular disease under hypercholesterolemia is due to associations between oxidized low-density lipoprotein (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) and between ox-LDL and coagulant profiles. We investigated the impact of different ox-LDL levels on coagulation time and plasma metabolomes in subjects with borderline hypercholesterolemia.One hundred thirty-one subjects with borderline hypercholesterolemia (serum cholesterol ≥200 mg/dL) were divided into low ox-LDL (n = 66) and high ox-LDL (n = 65) groups. After adjusting for confounding factors, the high ox-LDL group exhibited a significantly decreased activated partial thromboplastin time (aPTT) and prothrombin time (PT) and increased Lp-PLA2 activity. Compared to the low ox-LDL group, the high ox-LDL group exhibited significantly increased intensities of 17 lysophosphatidylcholines (lysoPCs) and 7 lysophosphatidylethanolamines (lysoPEs). Ox-LDL was inversely correlated with aPTT and PT and positively correlated with Lp-PLA2 activity. Positive correlations were also found among ox-LDL, Lp-PLA2 activity, lysoPCs, and lysoPEs. LysoPCs and lysoPEs were inversely correlated with PT and aPTT. The identified plasma metabolites, including amino acids, fatty acid amides, acylcarnitines, and lysophospholipids, were significantly upregulated in the high ox-LDL group.High ox-LDL levels may be involved in the development of a procoagulant state in subjects with borderline hypercholesterolemia by increasing Lp-PLA2 activity and lysoPC and lysoPE levels.