[Early intervention on atherosclerosis by fluvastatin and lectin-like oxidized low-density lipoprotein receptor-1 expression in atherosclerotic arteries in immature rabbits].
OBJECTIVE
The present study was designed to investigate the preventive and therapeutic effect of 3-hydroxy-3-methylglutanyl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin on the development of atherosclerosis (AS) in immature rabbits and its possible mechanism by detecting the expression level of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the abdominal aorta.


METHODS
A model of hypercholesterolemia (HC) was established by high-cholesterol diet and 24 immature rabbits were divided randomly and equally into control group, HC-diet group and fluvastatin group. At the beginning of the study and after 12 weeks, the body height (BH) and body weight (BW) of the rabbits were measured and their body mass index (BMI) was calculated. At the end of 12 weeks, serum total cholesterol (TC) and low-density lipoprotein (LDL) levels were examined. The intima-medial thickness of the abdominal aorta (aIMT) was measured by using non-invasive high-resolution (14 MHz) B-mode ultrasound imaging. Histological changes in abdominal arteries were studied by H&E-staining and histomorphometric analysis. The gene expression of LOX-1 in abdominal aorta was evaluated by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and its protein expression was examined by immunohistochemistry.


RESULTS
High cholesterol diet induced hypercholesterolemia and early AS in immature rabbits. In HC-diet group serum TC and LDL levels in rabbits elevated. B mode echocardiography showed that aIMT was thickened and pathomorphology indicated that extensive aortic intima (I) and intima and media (I + M) became thickened and the ratio of the area of intima to media (S(I)/S(M)) was increased. Aortic intimal proliferation in HC-diet group was associated with a marked increase in LOX-1 expression (protein and mRNA) in endothelium and neointima of the abdominal aorta. Treatment with fluvastatin at a dosage of 10 mg/(kg.d) deduced serum lipid, attenuated artery intimal proliferation and markedly decreased the enhanced LOX-1 expression level in endothelium and neointima in immature rabbits. There were no significant differences of BH, BW or BMI among the three groups.


CONCLUSIONS
These findings suggested that early treatment with fluvastatin not only induced a significant regression of arterial lesions of HC and early AS in immature rabbits, but also had a crucial endothelial protective effect by down-regulating LOX-1 expression level in atherosclerotic arteries in early AS.
Yu
Yong-hui
YH
Department of Pediatrics, Shandong Provincial Hospital, Shandong University, Jinan 250021, China.
Wang
Yi
Y
Chen
Yao
Y
Liu
Zhong-zhi
ZZ
Sun
Shu-zhen
SZ
Meng
Xiao-hui
XH
D000818:Animals; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging / Q000473:pathology; D001158:Arteries / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL / Q000097:blood; D004452:Echocardiography; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D011817:Rabbits; D051127:Scavenger Receptors, Class E / Q000378:metabolism*
D002791:Cholesterol, Dietary; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D051127:Scavenger Receptors, Class E; D000077340:Fluvastatin