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Lipid transfer proteins: Past, present and perspectives

      Abstract

      Lipid transfer proteins (PLTP and CETP) play roles in atherogenesis by modifying the arterial intima cholesterol content via altering the concentration and function of plasma lipoproteins and influencing inflammation. In this regard, endotoxins impair the reverse cholesterol transport (RCT) system in an endotoxemic rodent model, supporting a pro-inflammatory role of HDL reported in chronic diseases where atherosclerosis is premature. High PLTP activity related to atherosclerosis in some clinical studies, but the mechanisms involved could not be ascertained. In experimental animals the relation of elevated plasma PLTP concentration with atherosclerosis was confounded by HDL-C lowering and by unfavorable effects on several inflammatory markers. Coincidently, PLTP also increases in human experimental endotoxemia and in clinical sepsis. Human population investigations seem to favor low CETP as atheroprotective; this is supported by animal models where overexpression of huCETP is atherogenic, most likely due to increased concentration of apoB-lipoprotein-cholesterol. Thus, in spite of CETP facilitating the HDL-C-mediated RCT, the reduction of apoB-LP-cholesterol concentration is the probable antiatherogenic mechanism of CETP inhibition. On the other hand, experimental huCETP expression protects mice from the harmful effects of a bacterial polysaccharide infusion and the mortality rate of severely ill patients correlates with reduction of the plasma CETP concentration. Thus, the roles played by PLTP and CETP on atherosclerosis and acute inflammation seem contradictory. Therefore, the biological roles of PLTP and CETP must be carefully monitored when investigating drugs that inhibit their activity in the prevention of atherosclerosis.

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