Pravastatin inhibits expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in Watanabe heritable hyperlipidemic rabbits: a new pleiotropic effect of statins.
BACKGROUND
LOX-1, a receptor for oxidized low-density lipoprotein (OxLDL), seems to play a critical role in foam cell formation of macrophages (Mphis) and smooth muscle cells (SMC). Inhibition of LOX-1 expression reduces foam cell formation and might influence lipid core formation in atherosclerotic lesions. Because statins are able to downregulate LOX-1 expression in vitro, we examined if pravastatin can be used to reduce LOX-1 expression and lipid core formation in lesions of Watanabe heritable hyperlipidemic (WHHL) rabbits.


RESULTS
Pravastatin downregulated LOX-1 expression in cultured human Mphis and in cultured human aortic SMCs. Homozygous WHHL rabbits were treated with 50 mg kg(-1) d(-1) pravastatin for 32 weeks. Immunohistochemical studies revealed that LOX-1 was expressed in intimal Mphis and SMCs of atherosclerotic lesions. The pravastatin-treated rabbits showed, compared with untreated rabbits, a significantly reduced LOX-1 protein and mRNA expression in the aortic arch. Lipid labeling of this aorta region also demonstrated a strong reduction of the ratio of lipid core area/total lesion area in pravastatin-treated rabbits.


CONCLUSIONS
The in vivo inhibition of LOX-1 expression by pravastatin demonstrated here represents a new pleiotropic effect of pravastatin. This in vivo inhibition of LOX-1 might be one mechanism for the lipid core reducing effect of pravastatin in atherogenesis.
Hofnagel
Oliver
O
Leibniz-Institute for Arteriosclerosis Research, University Hospital of Muenster, Germany. hofnagel@uni-muenster.de
Luechtenborg
Birgit
B
Eschert
Heike
H
Weissen-Plenz
Gabriele
G
Severs
Nicholas J
NJ
Robenek
Horst
H
D000818:Animals; D001011:Aorta / Q000473:pathology; D001018:Aortic Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D017035:Pravastatin / Q000494:pharmacology*; D011817:Rabbits; D051127:Scavenger Receptors, Class E / Q000235:genetics*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D051127:Scavenger Receptors, Class E; D002784:Cholesterol; D017035:Pravastatin