Objective-Plasma phospholipid transfer protein (PLTP) is involved in intravascular lipoprotein metabolism. PLTP is known to act through 2 main mechanisms: by remodeling high-density lipoproteins (HDL) and by increasing apolipoprotein (apo) B-containing lipoproteins. The aim of this study was to generate a new model of human PLTP transgenic (HuPLTPTg) rabbit and to determine whether PLTP expression modulates atherosclerosis in this species that, unlike humans and mice, displays naturally very low PLTP activity. Methods and Results-In HuPLTPTg rabbits, the human PLTP cDNA was placed under the control of the human eF1-␣ gene promoter, resulting in a widespread tissue expression pattern and in increased plasma PLTP. The HuPLTPTg rabbits showed a significant increase in the cholesterol content of the plasma apoB-containing lipoprotein fractions, with a more severe trait when animals were fed a cholesterol-rich diet. In contrast, HDL cholesterol level was not modified in HuPLTPTg rabbits. Formation of aortic fatty streaks was increased in hypercholesterolemic HuPLTPTg animals as compared with nontransgenic littermates. Key Words: atherosclerosis Ⅲ lipoproteins Ⅲ metabolism Ⅲ transgenic models H uman plasma contains 2 distinct lipid transfer proteins (cholesteryl ester transfer protein [CETP] and phospholipid transfer protein [PLTP]) that promote the rapid exchange of lipid species between circulating lipoproteins, as well as between circulating lipoproteins and cells. 1 Although most reported data agree that the putative implication of CETP in lipoprotein metabolism and atherosclerotic process mostly concerns the net transfer of cholesteryl esters from antiatherogenic high-density lipoproteins (HDL) to potentially atherogenic apolipoprotein (apo) B-containing lipoproteins, 1 the precise function of PLTP and its consequences in terms of atherogenesis remain a matter of debate. PLTP was identified initially for its ability to promote the transfer of phospholipids from triglyceride-rich lipoproteins to HDL in the postprandial phase. 2 Subsequent studies reported that PLTP is also a key player in the HDL conversion process, leading to the emergence of large and small HDL products. 3,4 Recently, PLTP in human plasma was shown to reside mainly on lipid-poor complexes in association with proteins linked to immunity and inflammation, suggesting that the biological function of PLTP is rather complex in nature. 5 In support of this view, PLTP expression in the mouse was found to increase the production of apoB-containing lipoproteins by the liver 6 and intestine, 7 to decrease very low density lipoprotein (VLDL) catabolism, 8 to reduce the antioxidant protection of atherogenic lipoproteins, 9,10 to trigger inflammation, 11 and to promote the association of lipopolysaccharides with circulating lipoproteins. 12 All these properties have long been shown to influence the atherosclerotic process, whether acting individually or in a combined manner.
Conclusion-HumanHigh plasma PLTP concentrations were earlier reported in diabetic...