Altered Activities of Anti-atherogenic Enzymes Lecithin:cholesterol Acyltransferase, Paraoxonase and Platelet-activating Factor Acetylhydrolase in Atherosclerosis Susceptible Mice

We examined whether the putative anti-atherogenic enzymes lecithin:cholesterol acyltransferase (LCAT), paraoxonase 1 (PON) and platelet-activating factor acetylhydrolase (PAF-AH) are impaired in 8 week old atherosclerosis susceptible Apoe-/and Ldlr-/mice and whether plasma concentrations of bioactive oxidized phospholipids accumulate in plasma. Apoe-/mice had reduced (28%) LCAT activity and elevated LysoPC and bioactive oxidized phospholipids (POVPC and PGPC) compared to controls on the chow diet. Elevated oxidized phospholipids and reduced LCAT activity may, in part, contribute to spontaneous lesions in these mice on chow diet. A Western diet decreased LCAT activity further (50% of controls) and PON activity was decreased 38%. The Ldlr-/mice showed normal LCAT activity on chow diet and little accumulation of oxidized phospholipids. On a Western diet Ldlr-/mice had reduced LCAT activity (21%), but no change in PON activity. All genotypes had reduced PAF-AH activity on the Western diet. Apoe-/and Ldlr-/mice, but not controls, had elevated plasma bioactive oxidized phospholipids on the Western diet. We conclude that impairment of LCAT activity and accumulation of oxidized phospholipids are part of an early atherogenic phenotype in these models.