Erythrocyte membrane cholesterol and lipid core growth in a rabbit model of atherosclerosis: modulatory effects of rosuvastatin.
BACKGROUND
Lipid core expansion is partly responsible for the conversion of a stable atherosclerotic lesion to a rupture-prone plaque. Intraplaque hemorrhage contributes to the accumulation of cholesterol within unstable plaques. In the present study, we investigated, using a rabbit model of atherosclerosis, the extent to which diet-induced increases in cholesterol content of erythrocyte membranes (CEM) contribute to lipid core expansion and the modulatory effect of rosuvastatin use.


RESULTS
Rabbits fed with atherogenic diet (0.75% cholesterol) for 5 months exhibited advanced atherosclerotic lesions (mean plaque area, 0.39 ± 0.03 mm(2)), and lipid core size was associated with the concentration-time integral (CTI) of CEM levels (r=0.567, P=0.004) independent of other established predictors of lipid core size. Further experiments were performed by feeding rabbits atherogenic diet (1% cholesterol) for 3 months, followed by either normal diet or normal diet plus rosuvastatin for the next 3 months. Although no differences were observed in total plaque area between both groups, administration of rosuvastatin was associated with significantly smaller lipid cores, fewer macrophages within the lipid core, less microvessels as well as with lower CTI of CEM levels compared to normal diet alone. Moreover, intraplaque erythrocyte membranes covered a smaller lipid core area in rabbits under rosuvastatin plus normal diet as opposed to rabbits under diet alone.


CONCLUSIONS
Increased CEM levels, induced by high-cholesterol diet, are associated with lipid core growth. Ingestion of a potent HMG-CoA reductase inhibitor (rosuvastatin) may decrease CEM levels, and this effect may contribute to regression of the lipid core.
University Cardiology Department, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. Electronic address: dtziakas@med.duth.gr.
Dimitrios
D
Tziakas
Georgios
G
Chalikias
Alkistis
A
Kapelouzou
Ioannis
I
Tentes
Katrin
K
Schäfer
Panagiotis
P
Karayannakos
Alkiviadis
A
Kostakis
Harissios
H
Boudoulas
Stavros
S
Konstantinides
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002784:Cholesterol / Q000378:metabolism*; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005464:Fluorobenzenes / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008297:Male; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology*; D011817:Rabbits; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002784:Cholesterol
Atherosclerosis; Cholesterol; Erythrocyte membranes; Rabbits; Rosuvastatin