Ja. Joles et al., LIPOPROTEIN PHOSPHOLIPID-COMPOSITION AND LCAT ACTIVITY IN NEPHROTIC AND ANALBUMINEMIC RATS, Kidney international, 46(1), 1994, pp. 97-104
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.