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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1642.)
© 2001 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Markedly Elevated Lipid Transfer Inhibitor Protein in Hypercholesterolemic Subjects Is Mitigated by Plasma Triglyceride Levels

Richard E. Morton; Valéria Nunes; Lahoucine Izem; Eder Quintão

From the Department of Cell Biology (R.E.M., L.I.), Lerner Institute, Cleveland Clinic Foundation, Cleveland, Ohio, and the Lipids Laboratory (V.N., E.Q.), University of São Paulo Medical School, São Paulo, Brazil.

Correspondence to Richard E. Morton, PhD, Cell Biology, NC10, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. E-mail mortonr{at}ccf.org

Abstract—— Lipid transfer inhibitor protein (LTIP, apolipoprotein F) regulates the interaction of cholesteryl ester transfer protein (CETP) with lipoproteins and is postulated to enhance the ability of CETP to stimulate reverse cholesterol transport. The factors that regulate LTIP levels and control its biosynthesis are unknown. Here, we demonstrate that plasma LTIP is dramatically increased (3-fold) in hypercholesterolemic subjects with normal to mildly elevated plasma triglyceride (TG) levels compared with control subjects. LTIP in these subjects is not correlated with the extent of hypercholesterolemia or with low density lipoprotein (LDL), high density lipoprotein, or CETP levels. However, unlike CETP, LTIP levels correlate negatively with plasma TG levels. This association does not appear to reflect decreased LTIP synthesis, inasmuch as conditions that stimulate TG synthesis and secretion (200 µmol/L oleate) do not reduce LTIP secretion by SW872 or Caco-2 cells. In contrast, native or acetyl LDL stimulates LTIP secretion 2-fold. Importantly, although plasma LTIP typically resides on LDL, up to 25% of LTIP is bound to very low density lipoprotein when this lipoprotein is enriched in cholesteryl esters, as occurs in hypercholesterolemia. In summary, LTIP levels are markedly elevated by hypercholesterolemia; however, plasma TG levels attenuate this response. We hypothesize that this arises from an increased association of LTIP with very low density lipoprotein, leading to a more rapid clearance of the inhibitor from circulation.

Key Words: hypercholesterolemia • cholesteryl ester transfer protein • lipid transfer inhibitor protein • triglycerides • lipoprotein metabolism

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