The role of plasma phospholipid transfer protein (PLTP) in the development of atherosclerosis : studies in genetically modified mice

Complications of atherosclerosis are the principal cause of mortality in Western societies. Epidemiological studies have shown that a high HDL cholesterol level in plasma is inversely correlated with the risk for atherosclerosis. The exact biological mechanism behind this finding is not known. There are many factors that affect HDL metabolism. In vitro and in vivo studies demonstrated that plasma phospholipid transfer protein (PLTP) plays a major role in phospholipid transfer processes between lipoproteins, and also in modulating size and composition of HDL particles. The aim of this thesis was to clarify the role of PLTP in HDL metabolism and in the development of atherosclerosis. Normal mice lack cholesteryl ester transfer protein (CETP) and have very low LDL plasma levels compared with humans. Therefore we used a genetically modified mouse model with a humanlike lipoprotein profile. These animals are transgenic for CETP and carry one mutated allele of the LDL receptor (huCETPtg/LDL-R+I-).

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