title: Increased lipase inhibition in uremia: identification of pre-beta-HDL as a major inhibitor in normal and uremic plasma.
abstract: The hypertriglyceridemia commonly observed in uremia has been attributed to an abnormally high inhibitor activity in plasma for lipoprotein lipase (LPL) and hepatic lipase (HL), both of which have a key role in lipoprotein metabolism. The purpose of this investigation was to establish a relationship between plasma lipase inhibitor activity and hypertriglyceridemia, identify the main plasma lipase inhibitor, and determine the basis for the greater inhibitor activity in uremia. In a mixed population of normal (N = 8) and uremic subjects (N = 12), log-transformed plasma triglycerides correlated with both inhibitor activity and uremic status. However, inhibitor activity was the only retained predictor variable for triglycerides in a multiple linear regression model (r = 0.91; P < 0.0001). An inhibitor isolated from normal plasma was identified as a particle containing apolipoprotein A-I (apo A-I) and 3% phospholipid. This particle, which has pre-beta electrophoretic mobility and a Stokes' radius of 54 A, therefore corresponds to a form of the previously described pre-beta-HDL (free apo A-I) in the non-lipoprotein fraction of plasma. Comparison of normal and uremic plasma indicated that the greater lipase inhibitor activity in the latter could be attributed to an increased concentration of apo A-I in the non-lipoprotein fraction of plasma (pre-beta-HDL), as well as to increased inhibition by the uremic lipoproteins. The increased plasma lipase inhibitor activity may be important in the pathogenesis of hypertriglyceridemia in chronic renal failure.
authors.affiliation: Medical Service, Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Cheung
authors.forename: C J
authors.initials: CJ
authors.lastname: Parker
authors.forename: K
authors.initials: K
authors.lastname: Ren
authors.forename: P H
authors.initials: PH
authors.lastname: Iverius
mesh_terms: D004791:Enzyme Inhibitors / Q000097:blood / Q000302:isolation & purification; D053442:High-Density Lipoproteins, Pre-beta; D006801:Humans; D015228:Hypertriglyceridemia / Q000209:etiology; D008049:Lipase / Q000037:antagonists & inhibitors*; D008075:Lipoproteins, HDL / Q000097:blood* / Q000302:isolation & purification; D014280:Triglycerides / Q000097:blood; D014511:Uremia / Q000097:blood* / Q000150:complications / Q000201:enzymology*
chemical_list: D004791:Enzyme Inhibitors; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D014280:Triglycerides; D008049:Lipase