LIPOPROTEIN PHOSPHOLIPID-COMPOSITION AND LCAT ACTIVITY IN NEPHROTIC AND ANALBUMINEMIC RATS

Albumin is an acceptor of lysophosphatidylcholine (LPC), product of th e lecithin:cholesterol acyl transferase (LCAT) reaction, and it has be en suggested that low LCAT activity and reduced cholesterol esterifica tion rate in patients with the nephrotic syndrome may be linked to dep letion of albumin. Effects of low plasma albumin levels on LCAT activi ty, cholesterol esterification rates and LPC-binding were therefore st udied in hyperlipidemic nephrotic (NS) and analbuminemic (NAR) rats. L PC-binding was also measured in normoalbuminemic rats with dietary hyp ercholesterolemia. Remarkably, LCAT activity, measured with excess exo genous substrate, was not decreased but increased in both NAR and NS r ats. Molar esterification rates with endogenous substrate were increas ed in NAR but normal in NS rats. In normoalbuminemic rats, with or wit hout 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 mark ed contrast to normoalbuminemic rats, decreased in lipoprotein-deficie nt plasma. Phosphatidylcholine, quantitatively the major phospholipid, was distributed proportionally over the lipoproteins in NS, NAR and c ontrol rats. Therefore, in hypoalbuminemia and analbuminemia LPC is ma inly bound to lipoproteins, which is in contrast to the paucity of LPC in these particles in normoalbuminemic rats. Cholesterol esterificati on in nephrotic plasma is thus not impaired by lack of an acceptor for LPC-binding. The absence of an increase in molar cholesterol esterifi cation in conjunction with increased LCAT activity points to a possibl e defect of the substrate for this reaction in nephrotic plasma. Incre ased LPC levels in LDL, a characteristic of oxidized LDL, may be a hit herto unrecognized atherosclerotic risk factor in the nephrotic syndro me.