Lipoprotein phospholipid composition and LCAT activity in nephrotic and analbuminemic rats

Lipoprotein phospholipid composition and LCAT activity in nephrotic and analbuminemic rats. Albumin is an acceptor of lysophosphatidyl-choline (LPC), product of the lecithinxholesterol acyl transferase (LCAT) reaction, and it has been suggested that low LCAT activity and reduced cholesterol esterification rate in patients with the nephrotic syndrome may be linked to depletion of albumin. Effects of low plasma albumin levels on LCAT activity, cholesterol esterification rates and LPC-binding were therefore studied in hyperlipidemic nephrotic (NS) and analbuminemic (NAR) rats. LPC-binding was also measured in normoalbuminemic rats with dietary hypercholesterolemia. Remarkably, LCAT activity, measured with excess exogenous substrate, was not decreased but increased in both NAR and NS rats. Molar esterification rates with endogenous substrate were increased in NAR but normal in NS rats. In normoalbuminemic rats, with or without hypercholesterolemia, LPC was primarily found in the lipoprotein-deficient plasma and the HDL3 fraction. In NAR and NS rats LPC levels were increased in lipoproteins (notably in LDL and HDL2), but, in marked contrast to normoalbuminemic rats, decreased in lipoprotein-deficient plasma. Phosphatidylcholine, quantitatively the major phospholipid, was distributed proportionally over the lipoproteins in NS, NAR and control rats. Therefore, in hypoalbuminemia and analbuminemia LPC is mainly bound to lipoproteins, which is in contrast to the paucity of LPC in these particles in normoalbuminemic rats. Cholesterol esterification in nephrotic plasma is thus not impaired by lack of an acceptor for LPC-binding. The absence of an increase in molar cholesterol esterification in conjunction with increased LCAT activity points to a possible defect of the substrate for this reaction in nephrotic plasma. Increased LPC levels in LDL, a characteristic of oxidized LDL, may be a hitherto unrecognized atherosclerotic risk factor in the nephrotic syndrome