Hyperlipoproteinemia in Nagase analbuminemic rats: effects of pravastatin on plasma (apo)lipoproteins and lecithin:cholesterol acyltransferase activity.
The present study demonstrates very high levels of plasma lipids and high density lipoprotein (HDL) apolipoproteins (apoA-I and apoE) in female Nagase analbuminemic rats (NAR) fed a semi-synthetic diet in order to further increase the hyperlipidemia present in this strain. Plasma apoB-containing lipoproteins (very low, intermediate, and low density lipoproteins) were also elevated in NAR. Plasma cholesterol was mainly present in lipoprotein particles with a density between 1.02 and 1.12 g/ml. Separation of lipoprotein classes by gel filtration showed that the major cholesterol-carrying lipoprotein fractions in NAR plasma are apoE-rich HDL and apoA-I-rich HDL. The high HDL levels in NAR are explained, at least partly, by the two- to threefold elevated activity of plasma lecithin:cholesterol acyltransferase (LCAT). The lysophosphatidylcholine generated in the LCAT reaction, as well as plasma free fatty acids, are bound to lipoproteins in NAR plasma. A study was carried out to determine whether the elevated LDL and aopoE-rich HDL levels could be corrected by administration of the HMG-CoA reductase inhibitor pravastatin (at a dose of 1 mg/kg per day). Pravastatin treatment results in a 43% decrease in plasma triglycerides in NAR, but not in Sprague-Dawley (SDR) rats, and had no significant effect on plasma total cholesterol, phospholipids apolipoproteins A-I, A-IV, B, or E, as well as on plasma LCAT activity levels in NAR or SDR.
Van Tol
A
A
Department of Biochemistry, Erasmus University, Rotterdam, The Netherlands.
Jansen
E H
EH
Koomans
H A
HA
Joles
J A
JA
D000818:Animals; D001053:Apolipoproteins / Q000097:blood*; D002850:Chromatography, Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006951:Hyperlipoproteinemias / Q000097:blood*; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D010743:Phospholipids / Q000097:blood; D017035:Pravastatin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D001053:Apolipoproteins; D005230:Fatty Acids, Nonesterified; D010743:Phospholipids; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D017035:Pravastatin