Tanshinone II-A attenuates and stabilizes atherosclerotic plaques in Apolipoprotein-E knockout mice fed a high cholesterol diet

Xu, Suowen, Little, Peter J., Lan, Tian, Huang, Yan, Le, Kang, Wu, Xiaoqian, Shen, Xiaoyan, Huang, Heqing, Cai, Yi, Tang, Futian, Wang, Hua and Liu, Peiqing (2011) Tanshinone II-A attenuates and stabilizes atherosclerotic plaques in Apolipoprotein-E knockout mice fed a high cholesterol diet. Archives of Biochemistry and Biophysics, 515 1-2: 72-79. doi:10.1016/j.abb.2011.08.006


Author Xu, Suowen
Little, Peter J.
Lan, Tian
Huang, Yan
Le, Kang
Wu, Xiaoqian
Shen, Xiaoyan
Huang, Heqing
Cai, Yi
Tang, Futian
Wang, Hua
Liu, Peiqing
Title Tanshinone II-A attenuates and stabilizes atherosclerotic plaques in Apolipoprotein-E knockout mice fed a high cholesterol diet
Journal name Archives of Biochemistry and Biophysics   Check publisher's open access policy
ISSN 0003-9861
1096-0384
Publication date 2011-11
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.abb.2011.08.006
Open Access Status Not yet assessed
Volume 515
Issue 1-2
Start page 72
End page 79
Total pages 8
Place of publication Maryland Heights, MO, United States
Publisher Academic Press
Language eng
Formatted abstract
Tanshinone II-A (Tan), a bioactive diterpene isolated from Salvia miltiorrhiza Bunge (Danshen), possesses anti-oxidant and anti-inflammatory activities. The present study investigated whether Tan can decrease and stabilize atherosclerotic plaques in Apolipoprotein-E knockout (ApoE -/-) mice maintained on a high cholesterol diet (HCD). Six week-old mice challenged with a HCD were randomly assigned to 4 groups: (a) C57BL/6J; (b) ApoE-/-; (c) ApoE-/- + Tan-30 (30 mg/kg/d); (d) ApoE-/- + Tan-10 (10 mg/kg/d). After 16 weeks of intervention, Tan treated mice showed decreased atherosclerotic lesion size in the aortic sinus and en face aorta. Furthermore, immunohistochemical analysis revealed that Tan rendered the lesion composition a more stable phenotype as evidenced by reduced necrotic cores, decreased macrophage infiltration, and increased smooth muscle cell and collagen contents. Tan also significantly reduced in situ superoxide anion production, aortic expression of NF-κB and matrix metalloproteinase-9 (MMP-9). In vitro treatment of RAW264.7 macrophages with Tan significantly suppressed oxidized LDL-induced reactive oxygen species production, pro-inflammatory cytokine (IL-6, TNF-α, MCP-1) expression, and MMP-9 activity. Tan attenuates the development of atherosclerotic lesions and promotes plaque stability in ApoE-/- mice by reducing vascular oxidative stress and inflammatory response. Our findings highlight Tan as a potential therapeutic agent to prevent atherosclerotic cardiovascular diseases.
Keyword ApoE -/- mice
Atherosclerosis
NF-κB
Plaque composition
Reactive oxygen species
Tanshinone
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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