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Updated: Jun 8, 2026

Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Tanshinone IIA attenuates atherosclerosis in ApoE(-/-) mice through down-regulation of scavenger receptor expression
Fu-Tian Tang1, Yuan Cao, Tie-Qiao Wang
1Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
Abstract:
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.
Insights
Tanshinone IIA (TSIIA) protects against atherosclerosis in ApoE(-/-) mice by reducing lesions and cholesterol. It also down-regulates scavenger receptors like CD36, potentially via PPARγ antagonism, offering a novel therapeutic avenue.
Area of Science:
- Pharmacology and Toxicology
- Cardiovascular Research
- Molecular Biology
Background:
- Atherosclerosis is a complex inflammatory disease driven by lipid accumulation and scavenger receptor activity.
- Apolipoprotein E deficient (ApoE(-/-)) mice are a standard model for studying atherosclerosis.
- Scavenger receptors, including CD36 and scavenger receptor-A (SR-A), play critical roles in atherogenesis by mediating oxidized LDL uptake.
Purpose of the Study:
- To investigate the protective effects of tanshinone IIA (TSIIA) against atherosclerosis in ApoE(-/-) mice.
- To elucidate the underlying mechanisms, focusing on the regulation of scavenger receptors (SR-A and CD36) and related pathways.
- To explore the role of peroxisome proliferator-activated receptor gamma (PPARγ) in TSIIA's action.
Main Methods:
- In vivo studies using ApoE(-/-) mice treated with varying doses of TSIIA.
- In vitro studies using mouse peritoneal macrophages exposed to oxidized LDL (oxLDL).
- Analysis of atherosclerotic lesions, cholesterol levels, CD68 expression, and mRNA/protein levels of CD36, SR-A, and PPARγ.
Main Results:
- TSIIA significantly inhibited atherosclerotic lesions, reduced aortic cholesterol, and decreased CD68 expression in ApoE(-/-) mice.
- TSIIA lowered serum oxidized LDL (oxLDL) levels and down-regulated CD36, SR-A, and PPARγ mRNA in mouse aortas.
- In macrophages, TSIIA reduced oxLDL uptake, cholesterol levels, and CD36 expression, with evidence suggesting PPARγ antagonism is involved.
Conclusions:
- Tanshinone IIA exhibits significant anti-atherosclerotic effects in ApoE(-/-) mice.
- These protective effects are associated with the down-regulation of scavenger receptors (CD36) and potentially mediated by anti-oxidative properties and PPARγ antagonism.
- TSIIA represents a potential therapeutic agent for atherosclerosis, warranting further investigation.
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