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Tetramethylpyrazine inhibits agiontensin H--induced nudear factor--#kappa#B activation and bone morphogenetic protein--2 downregulation in rat vascular smooth muscle cells

Ren Xinyu, Ruan Qiurong, Zhu Dahe, Zhu Min, Qu Zhiling, Lu Jun

Department of Pathology, Tongji Medical College of Huazhong University of Science and Technology.Wuhan 430030,Hubei

Abstract

Tetramethylpyrazine （TMP）, an effective component of traditional Chinese medicine Chuanxiong, is commonly used to resolve embolism. Its possible therapeutic effect against atherosclerosis has received considerable attention recently. Angiotensin Ⅱ （Ang Ⅱ） is highly implicated in the proliferation of vascular smooth muscle cells （VSMCs）, resulting in atherosclerosis. The mechanisms of TMP in the proliferation of VSMCs induced by Ang H remain to be defined. The present study was aimed to study the effect of TMP on Ang Ⅱ-induced VSMC proliferation through detection of nuclear factor-#kappa#B （NF-#kappa#B） activity and bone morphogenetic protein-2 （BMP-2） expression. Primary cultured rat aortic smooth muscle cells were divided into the control group, Ang Ⅱ group, Ang Ⅱ + TMP group and TMP group. Cells in each group were harvested at different time points （15, 30 and 60 min for detection of NF-#kappa#B activity; 6, 12 and 24 h for measurement of BMP-2 expression）. NF-#kappa#B activation was identified as nuclear staining by irnmtmohistochemistry. BMP-2 expression was observed through Western blot, immunohistochemistry and in situ hybridization. The results showed that： （1） Ang Ⅱ stimulated the activation of NF-#kappa#B. Translocation of NF-#kappa#B p65 subunit from cytoplasm to nucleus appeared as early as 15 min, peaked at 30 min （P〈0.01） and declined after 1 h. （2） TMP inhibited Ang H-induced NF-#kappa#B activation （P〈 0.01）. （3） Ang H increased BMP-2 expression at 6 h but declined it significantly at 12 and 24 h （P〈0.01）. （4） BMP-2 expression was also kept at high level at 6 h in Ang Ⅱ + TMP group but maintained at the normal level at 12 and 24 h. （5） There was no significant difference in NF-#kappa#B activation and BMP-2 expression between the control group and TMP group. These results indicate that TMP inhibits Ang Ⅱ-induced VSMC proliferation through repression of NF-#kappa#B activation and BMP-2 reduction, and BMP-2 expression is independent of the NF-#kappa#B pathway. In conclusion, TMP has therapeutic potential for the treatment of atherosclerosis.

Key words: bone morphogenetic protein-2;nuclear factor-#kappa#B;angiotensinⅡ;Atherosclerosis;Tetramethylpyrazine

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Citing This Article：

Ren Xinyu, Ruan Qiurong, Zhu Dahe, Zhu Min, Qu Zhiling, Lu Jun. Tetramethylpyrazine inhibits agiontensin H--induced nudear factor--#kappa#B activation and bone morphogenetic protein--2 downregulation in rat vascular smooth muscle cells. Acta Physiol Sin 2007; 59 (3): 339-344 (in Chinese with English abstract).