Decreased activation of lecithin:cholesterol acyltransferase by glycated apolipoprotein A-I

Non-enzymatic glycation of plasma proteins may contribute to the excess risk of developing atherosclerosis in patients with diabetes mellitus. Glycated apolipoprotein A-I isolated from diabetic subjects was tested in vitro for its ability to activate lecithin:cholesterol acyltransferase, the principal cholesterol-esterifying enzyme in plasma. Activation by glycated apolipoprotein A-I was significantly lower at all concentrations than the activation by normal apolipoprotein A-I. Linear regression analysis of the kinetic data shows that the ratio app Vmax/app Km was significantly lower (p < 0.01) for glycated apolipoprotein A-I (0.29 nmol.l/h.mumol) than for normal apolipoprotein A-I (0.78 nmol.l/h.mumol). Because lecithin:cholesterol acyltransferase provides a driving force in reverse cholesterol transport by esterifying the cellular cholesterol removed by HDL, it is tempting to postulate that this abnormal activation may be associated with a reduction in reverse cholesterol transport and associated with the accelerated development of atherosclerosis in diabetic patients.