Increased lipase inhibition in uremia: identification of pre-beta-HDL as a major inhibitor in normal and uremic plasma.
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.
Cheung
A K
AK
Medical Service, Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
Parker
C J
CJ
Ren
K
K
Iverius
P H
PH
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*
D004791:Enzyme Inhibitors; D053442:High-Density Lipoproteins, Pre-beta; D008075:Lipoproteins, HDL; D014280:Triglycerides; D008049:Lipase