Tanshinone IIA attenuates atherosclerosis in ApoE(-/-) mice through down-regulation of scavenger receptor expression.
This study is designed to investigate the protection of tanshinone IIA (TSIIA) against atherosclerosis in apolipoprotein E deficient (ApoE(-/-)) mice and to explore the mechanisms by focusing on the expressions of scavenger receptors, scavenger receptor-A (SR-A) and CD36. The in vivo study demonstrated that TSIIA (10-90mg/kg) inhibited the atherosclerotic lesions, down-regulated the CD68 protein expression in lesion and decreased the contents of cholesterol in aortas of ApoE(-/-) mice. In addition, TSIIA reduced the serum levels of oxidized LDL (oxLDL) and down-regulated the mRNA expression of CD36, SR-A and peroxisome proliferator-activated receptor gamma (PPARγ) in aortas. The in vitro study showed that TSIIA (0.1-10μM) decreased cholesterol level and DiI-oxLDL uptake in mouse peritoneal macrophages treated with oxLDL (50μg/ml). In addition, TSIIA down-regulated the mRNA and protein expression of CD36 but not that of SR-A in oxLDL treated macrophages. TSIIA also down-regulated the mRNA expression of PPARγ in oxLDL treated macrophages. Furthermore, TSIIA reduced the mRNA expression of CD36 in macrophages treated with PPARγ agonist 15d-PGJ(2) (2μM) or troglitazone (50μM), whereas both 15d-PGJ(2) (0.5-1.5μM) and troglitazone (5-20μM) dose-dependently abolished the down-regulation of CD36 expression by TSIIA in oxLDL treated macrophages. These results suggest that TSIIA attenuates the atherosclerotic lesion in ApoE(-/-) mice, which might be attributed to the properties of both anti-oxidation and down-regulation of scavenger receptors. Furthermore, antagonism of PPARγ might be involved in the down-regulation of CD36 by TSIIA.
Tang
Fu-Tian
FT
Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
Cao
Yuan
Y
Wang
Tie-Qiao
TQ
Wang
Li-Jing
LJ
Guo
Jiao
J
Zhou
Xiao-Shi
XS
Xu
Suo-Wen
SW
Liu
Wei-Hua
WH
Liu
Pei-Qing
PQ
Huang
He-Qing
HQ
D045784:Abietanes; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001021:Aortic Valve / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D051379:Mice; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000235:genetics* / Q000378:metabolism*; D000097382:CD68 Molecule
D045784:Abietanes; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001057:Apolipoproteins E; D018955:CD36 Antigens; D002784:Cholesterol; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D047495:PPAR gamma; D010616:Phenanthrenes; D012333:RNA, Messenger; D051117:Scavenger Receptors, Class A; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C099252:oxidized low density lipoprotein; C021751:tanshinone