Elevated expression of PLTP is atherogenic in apolipoprotein E deficient mice

AbstractObjectivePlasma phospholipid transfer protein (PLTP) plays a key role in lipoprotein metabolism. Its exact function in the development of atherosclerosis is still under debate however. We studied the effect of elevated PLTP expression in one of the most commonly used models of atherosclerosis, the ApoE deficient mouse.MethodsExperiment 1: Plasma PLTP activity, total cholesterol, HDL cholesterol and atherosclerosis development was measured in ApoE deficient mice with or without elevated expression of PLTP. Experiment 2: The same parameters were measured in ApoE deficient mice after bone marrow transplantation from wild type mice or mice with elevated PLTP expression. Experiment 3: Similar to experiment 2, but using donor mice with an ApoE deficient background.ResultsExperiment 1: ApoE deficient mice have more than two times more atherosclerosis when overexpressing PLTP and a strongly decreased plasma level of HDL. Experiment 2: Bone marrow transplantation with ApoE proficient cells results in a strong reduction of plasma cholesterol in ApoE deficient acceptor mice. Still, elevated PLTP in bone marrow derived cells evoke a reduction of HDL cholesterol and increased atherosclerosis. Experiment 3: Bone marrow transplantation with ApoE deficient cells results in much higher cholesterol levels, but here too HDL cholesterol levels are reduced and atherosclerosis increased.ConclusionIn all the models with ApoE deficiency, elevated PLTP expression causes higher levels of diet-induced atherosclerosis coinciding with decreased plasma levels of HDL cholesterol