Fluvastatin prevents renal injury and expression of lactin-like oxidized low-density lipoprotein receptor-1 in rabbits with hypercholesterolemia.
BACKGROUND
Lipid abnormalities are often complicated by renal dysfunction. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are the first-line choice for lowering cholesterol levels. The present study was designed to investigate whether statins could prevent and invert the development of renal injury in cholesterol-fed rabbits and to find the possible mechanism of their effects by detecting gene and protein expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the renal artery.


METHODS
Twenty-four male New Zealand white rabbits were divided into three groups: (1) control group, regular granules chow; (2) HC-diet group, granules chow with 1% cholesterol and 5% lard oil; and (3) fluvastatin group, 1% cholesterol and 5% lard oil diet plus fluvastatin [10 mg.kg(-1).d(-1)]. After 16 weeks, serum total cholesterol (TC), low-density lipoprotein (LDL) and creatinine (Cr) levels were measured. Renal hemodynamics and function, mainly including glomerular filtration rate (GFR) in vivo were quantified using (99m)Tc-DTPA single photon emission computed tomograph ((99m)Tc-DTPA SPECT). The thickness of the renal artery intima was quantitated in HE-stained segments by histomorphometry. Gene expression of LOX-1 in the renal artery was examined by semi-quantitative RT-PCR and its protein expression was evaluated by immunohistochemistry.


RESULTS
High cholesterol diet induced hypercholesterolemia (HC) complicated by renal dysfunction with increased levels of serum lipid and Cr, decreased GFR and delayed excretion and extensively thickened renal arterial intima in the HC-diet group. Rabbits in the control group showed a minimal LOX-1 expression (mRNA and protein) in the endothelium and neointima of the renal artery. Intimal proliferation of the renal artery in the HC-diet group was associated with a marked increase of LOX-1 expression (protein and mRNA). Treatment with fluvastatin improved renal function, attenuated intimal proliferation of the renal artery and markedly decreased the enhanced LOX-1 expression in the endothelium and neointima of the renal artery in rabbits.


CONCLUSIONS
Fluvastatin treatment could prevent the development of renal injury in patients with HC and early atherosclerosis (AS). This beneficial effect might be mediated by its pleiotropic effects including a decrease in total cholesterol exposure level and prevention of LOX-1 expression in atherosclerotic arteries.
Yu
Yong-hui
YH
Department of Pediatrics, Shandong Provincial Hospital, Shandong University, Jinan 250021, China.
Wang
Yi
Y
Dong
Bo
B
Sun
Shu-zhen
SZ
Chen
Yao
Y
Meng
Xiao-hui
XH
Liu
Zhong-zhi
ZZ
D000818:Animals; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D011973:Receptors, LDL / Q000032:analysis* / Q000235:genetics; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D015899:Tomography, Emission-Computed, Single-Photon
D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D012333:RNA, Messenger; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E; D000077340:Fluvastatin; D002784:Cholesterol; D003404:Creatinine