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Tetramethylpyrazine Attenuates Atherosclerosis Development and Protects Endothelial Cells from ox-LDL

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Abstract

Purpose

We assessed whether tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii Franchat, attenuates atherosclerosis (AS) development in rabbits and protects endothelial cells injured by ox-LDL.

Methods

In vivo, rabbits subjected to atherosclerosis were treated with TMP (75 and 150 mg/kg) by oral gavage for 12 weeks. In vitro, rat aortic endothelial cells (RAECs) were stimulated by ox-LDL.

Results

TMP treatment with 75 and 150 mg/kg significantly reduced the relative atherosclerosis area ratio in the aorta (0.41 ± 0.042, 0.27 ± 0.047 vs. 0.66 ± 0.058 in AS), the ratio of intimal/medial thickness (0.54 ± 0.09, 0.39 ± 0.07 vs. 1.1 ± 0.3 in AS) and the number of monocytes in intimal (10.1 ± 2.8, 8.2 ± 2.0 vs. 14.1 ± 4.9 counts/mm2 in AS). TMP also decreased levels of TC (15 ± 4.2 to 6.1 ± 1.2 mmol/L), TG (1.8 ± 0.3 to 1.08 ± 0.24 mmol/L), LDL-C (20.1 ± 4.3 to 10.2 ± 1.6 mmol/L) and increased HDL-C levels (0.40 ± 0.08 to 0.85 ± 0.17 mmol/L) in atherosclerosis rabbit plasma. TMP decreased the MCP-1 (187.3 ± 38.4 to 86.1 ± 17.2 pg/ml) and ICAM-1 (350.6 ± 43.7 to 260.6 ± 46.1 pg/ml) levels in plasma and inhibited LOX-1 expression in the rabbit aortas. Moreover, our in vitro study revealed that TMP suppressed monocyte adhesion to RAECs, inhibited RAEC migration, and down-regulated MCP-1 and ICAM-1 expression in ox-LDL-injured RAECs. Likewise, TMP inhibited LOX-1 and 5-LOX expression, and prevented nuclear accumulation of RelA/p65 and IκB degradation in ox-LDL-injured RAECs. Furthermore, TMP suppressed ox-LDL-induced activations of p-ERK, p-p38, and p-JNK MAPK.

Conclusion

TMP produces a tangible protection in atherosclerosis and endothelial cells. TMP might be a potential protective agent for atherosclerosis.

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Abbreviations

TMP:

Tetramethylpyrazine

HCD:

high-cholesterol diet

ET-1:

endothelin

ICAM-1:

intercellular adhesion molecule-1

MCP-1:

monocyte chemoattractant protein-1

TC:

serum total cholesterol

TG:

triglyceride

LDL-C:

low-density lipoprotein-cholesterol

HDL-C:

high-density lipoprotein-cholesterol

RAECs:

rat aorta endothelial cells

FCS:

fetal calf serum

LOX-1:

lectin-like oxidized-low-density lipoprotein receptor-1

5-LOX:

5-lipoxygenase

ox-LDL:

oxidized-low-density lipoprotein

ROS:

reactive oxygen species

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Acknowledgments

This study was supported by the Central Public-Interest Scientific Institution Basal Research Fund 2010GJSSJKA03 and National Basic Research Program (973) of China 2010CB912003.

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Authors and Affiliations

  1. Department of Cadre Ward No. 3, the General Hospital of Jinan Military Area Command of PLA, Jinan, China

    Guo-feng Wang

  2. Department of Cell Biology, National Research Institute of Family Planning, 12 Dahuisi Road, Beijing, China, 100081

    Cui-ge Shi

  3. State Key Laboratory of Drug Metabolism Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing, China

    Mu-zhen Sun

  4. Key Laboratory of Molecular Biophysics of Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China

    Lei Wang

  5. The Fifth People’s Hospital of Jinan, Jinan, China

    Shu-xia Wu & Hao-feng Wang

  6. Department of Neurobiology, Capital Medical University, Beijing, China

    Zhi-qing Xu

  7. Institute of Biophysics, Chinese Academy of Science, 15 Datun Road, Beijing, China, 100101

    Dong-mei Chen

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  1. Guo-feng Wang
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  2. Cui-ge Shi
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Corresponding authors

Correspondence to Cui-ge Shi or Dong-mei Chen.

Additional information

Guo-feng Wang and Cui-ge Shi contributed equally to this work.

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Wang, Gf., Shi, Cg., Sun, Mz. et al. Tetramethylpyrazine Attenuates Atherosclerosis Development and Protects Endothelial Cells from ox-LDL. Cardiovasc Drugs Ther 27, 199–210 (2013). https://doi.org/10.1007/s10557-013-6440-6

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  • DOI: https://doi.org/10.1007/s10557-013-6440-6

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