Lipid transfer inhibitor protein activity deficiency in normolipidemic uremic patients on continuous ambulatory peritoneal dialysis.
We previously demonstrated that lipid transfer inhibitor protein (LTIP) is a potent modifier of lipid transfer protein (LTP) function in vitro. Based on these studies, we proposed that LTIP activity is an important determinant of lipoprotein size and composition, which leads to a stimulation of reverse cholesterol transport. To further evaluate this hypothesis, we have studied a normolipidemic, uremic patient population undergoing continuous ambulatory peritoneal dialysis (CAPD) that is deficient in LTIP activity (< 18% of control). LDL from CAPD plasma was triglyceride enriched; the diameters of both CAPD LDL and HDL were increased and CAPD HDL was dominated by the largest subfraction, HDL2b. In CAPD patients, the plasma cholesterol esterification rate was only 61% of control; this decrease was due mainly to the poor reactivity of CAPD lipoproteins. CAPD lipoprotein-deficient plasma promoted twofold greater transfer of radiolabeled cholesteryl ester (CE) between standard lipoproteins than control, although LTP itself was increased only 39%. This twofold increase was not equally expressed among individual lipoprotein classes; CE transfers involving LDL were increased 2.4-fold, whereas those not involving LDL were increased only 50%. In whole plasma, CE net mass transfer to VLDL was slightly increased in CAPD plasma; relative to their CE content, control HDL contributed twofold more CE mass to VLDL than control LDL, but in CAPD plasma this preferential transfer of CE from HDL was absent. Collectively, the aberrations in CAPD lipoprotein composition and metabolism are consistent with the hypothesized role of LTIP. The data further support the role of LTIP in modulating the participation of HDL in CE mass transfers to VLDL. This is the first report of LTIP activity deficiency in humans.
Serdyuk
A P
AP
Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, OH 44195, USA.
Morton
R E
RE
D002352:Carrier Proteins / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D004951:Esterification; D005260:Female; D006023:Glycoproteins / Q000097:blood / Q000172:deficiency*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008074:Lipoproteins / Q000097:blood / Q000145:classification / Q000172:deficiency; D008297:Male; D008875:Middle Aged; D010531:Peritoneal Dialysis, Continuous Ambulatory; D012016:Reference Values; D014511:Uremia / Q000097:blood* / Q000628:therapy*
D002352:Carrier Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008055:Lipids; D008074:Lipoproteins; D002784:Cholesterol