Tetramethylpyrazine Attenuates Atherosclerosis Development and Protects Endothelial Cells from ox-LDL
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ORIGINAL ARTICLE
Tetramethylpyrazine Attenuates Atherosclerosis Development and Protects Endothelial Cells from ox-LDL Guo-feng Wang & Cui-ge Shi & Mu-zhen Sun & Lei Wang & Shu-xia Wu & Hao-feng Wang & Zhi-qing Xu & Dong-mei Chen Published online: 31 January 2013 # Springer Science+Business Media New York 2013
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 oxLDL-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. Keywords Tetramethylpyrazine . Atherosclerosis . Endothelial cells . NF-κB . MAPK
Guo-feng Wang and Cui-ge Shi contributed equally to this work. G.-f. Wang Department of Cadre Ward No. 3, the General Hospital of Jinan Military Area Command of PLA, Jinan, China C.-g. Shi (*) Department of Cell Biology, National Research Institute of Family Planning, 12 Dahuisi Road, Beijing, China 100081 e-mail: [email protected]
S.-x. Wu : H.-f. Wang The Fifth People’s Hospital of Jinan, Jinan, China
Z.-q. Xu Department of Neurobiology, Capital Medical University, Beijing, China
M.-z. Sun State Key Laboratory of Drug Metabolism Hematological Pharmacology, Beijing Institute of Transfusion Medicine, Beijing, China L. Wang 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
D.-m. Chen (*) Institute of Biophysics, Chinese Academy of Science, 15 Datun Road, Beijing, China 100101 e-mail:
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