Effect of simvastatin treatment on plasma apolipoproteins and hepatic apolipoprotein mRNA levels in the genetically hypercholesterolemic rat (RICO).
The effects of long-term treatment with simvastatin on plasma lipoproteins, plasma apolipoproteins, and on hepatic apolipoprotein gene expression were evaluated in genetically hypercholesterolemic (RICO) rats. Simvastatin administration caused a decrease in plasma triglyceride and phospholipid concentrations. Plasma cholesterol concentration was not changed by simvastatin, but cholesterol distribution among plasma lipoproteins was altered. Plasma apo B, apo A-I, and apo A-IV concentrations were lowered by simvastatin treatment whereas plasma apo E concentration was not affected by this drug. In the liver, simvastatin treatment induced a significant decrease of apo E mRNA level but had no effect on apo B, apo A-I, and apo A-IV mRNA abundances. It appears that simvastatin may modify plasma apolipoprotein concentrations by influencing their hepatic synthesis at both pre- and posttranscriptional levels.
Felgines
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C
Laboratoire des Maladies Métaboliques, INRA, Theix, St Genès Champanelle, France.
Sérougne
C
C
Mathé
D
D
Mazur
A
A
Lutton
C
C
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D001059:Apoproteins / Q000097:blood* / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010743:Phospholipids / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019821:Simvastatin; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D001059:Apoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D008074:Lipoproteins; D010743:Phospholipids; D012333:RNA, Messenger; D014280:Triglycerides; D008148:Lovastatin; D019821:Simvastatin