Objective. Cholesteryl ester transfer protein (CETP) is a plasmaglycoprotein that catalyses the transfer of cholesteryl esters fromHDL to the other plasma lipoproteins. Genetic deficiency of CETPis one of the known causes of primary hyperalphalipoproteinemiaand represents a unique tool to evaluate how structural HDL alterationsimpact on HDL atheroprotective activity. Aim of the presentstudy was to assess the vasculoprotective activity of HDL isolatedfrom carriers of genetic CETP deficiency.Subjects and Methods. HDL and HDL subfractions were isolatedfrom carriers of the R37X, Q165X and IVS7+1 CETP mutations.HDL and HDL subfractions from carriers were tested fortheir protein/lipid composition and for their anti-inflammatory andNO-promoting activity in endothelial cells.Results. HDL and HDL3 from carriers proved to be as effectiveas control HDL in down-regulating cytokine-induced VCAM-1and in enhancing eNOS expression in endothelial cells. CarriersHDL2 were instead more effective than control HDL2 in inhibitingVCAM-1 and enhancing eNOS expression with a gene-dose dependenteffect. These findings appear to be related to the peculiar lipidcomposition and the very high content in apoE of the HDL2 particlesisolated from carriers of CETP deficiency. On the contrary,carrier HDL2 were less effective than control HDL2 in stimulatingeNOS activation, likely because of a reduced S1P content.Conclusions. Large, apoE enriched HDL that accumulate in geneticCETP deficiency are very efficient in maintaining endothelialcell homeostasis, supporting the use of pharmacological CETPinhibition to increase HDL levels and enhance HDL-mediated atheroprotection.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2011|