Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.

<h4>Background</h4>Tetramethylpyrazine (TMP) is one of the active ingredients extracted from the Chinese herb Chuanxiong, which has been used to treat cerebrovascular and cardiovascular diseases, pulmonary diseases and cancer. However, the molecular mechanisms underlying the actions of T...

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Autores principales:	Xiaoxiao Cai, Zhao Chen, Xueke Pan, Lei Xia, Pei Chen, Ying Yang, Huan Hu, Jing Zhang, Kaijing Li, Jian Ge, Keming Yu, Jing Zhuang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8fb29db02ea342ccbf0a52cd4278e556
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spelling	oai:doaj.org-article:8fb29db02ea342ccbf0a52cd4278e5562021-11-18T08:33:38ZInhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.1932-620310.1371/journal.pone.0088176https://doaj.org/article/8fb29db02ea342ccbf0a52cd4278e5562014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24505417/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Tetramethylpyrazine (TMP) is one of the active ingredients extracted from the Chinese herb Chuanxiong, which has been used to treat cerebrovascular and cardiovascular diseases, pulmonary diseases and cancer. However, the molecular mechanisms underlying the actions of TMP have not been fully elucidated. In a previous study we showed that TMP-mediated glioma suppression and neural protection involves the inhibition of CXCR4 expression. The SDF-1/CXCR4 axis plays a fundamental role in many physiological and pathological processes. In this study, we further investigated whether the regulation of the SDF-1/CXCR4 pathway is also involved in the TMP-mediated inhibition of neovascularization or fibrosis and improvement of microcirculation.<h4>Methodology/principal findings</h4>Using a scratch-wound assay, we demonstrated that TMP significantly suppressed the migration and tubule formation of the human umbilical vein endothelial cell line ECV304 in vitro. The expression of CXCR4 in ECV304 cells is notably down-regulated after TMP treatment. In addition, TMP significantly suppresses corneal neovascularization in a rat model of corneal alkali burn injury. The expression of CXCR4 on days 1, 3 and 7 post-injury was determined through RT-PCR analysis. Consistent with our hypotheses, the expression of CXCR4 in the rat cornea is significantly increased with alkali burn and dramatically down-regulated with TMP treatment. Moreover, TMP treatment significantly attenuates bleomycin-induced rat pulmonary fibrosis, while immunofluorescence shows a notably decreased amount of CXCR4-positive cells in the TMP-treated group. Furthermore, TMP significantly down-regulates the expression of CXCR4 in platelets, lymphocytes and red blood cells. Whole-blood viscosity and platelet aggregation in rats are significantly decreased by TMP treatment.<h4>Conclusions</h4>These results show that TMP exerts potent effects in inhibiting neovascularization, fibrosis and thrombosis under pathological conditions; thus, the underlying mechanism of TMP might partially contribute to the down-regulation of CXCR4.Xiaoxiao CaiZhao ChenXueke PanLei XiaPei ChenYing YangHuan HuJing ZhangKaijing LiJian GeKeming YuJing ZhuangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e88176 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xiaoxiao Cai Zhao Chen Xueke Pan Lei Xia Pei Chen Ying Yang Huan Hu Jing Zhang Kaijing Li Jian Ge Keming Yu Jing Zhuang Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.
description	<h4>Background</h4>Tetramethylpyrazine (TMP) is one of the active ingredients extracted from the Chinese herb Chuanxiong, which has been used to treat cerebrovascular and cardiovascular diseases, pulmonary diseases and cancer. However, the molecular mechanisms underlying the actions of TMP have not been fully elucidated. In a previous study we showed that TMP-mediated glioma suppression and neural protection involves the inhibition of CXCR4 expression. The SDF-1/CXCR4 axis plays a fundamental role in many physiological and pathological processes. In this study, we further investigated whether the regulation of the SDF-1/CXCR4 pathway is also involved in the TMP-mediated inhibition of neovascularization or fibrosis and improvement of microcirculation.<h4>Methodology/principal findings</h4>Using a scratch-wound assay, we demonstrated that TMP significantly suppressed the migration and tubule formation of the human umbilical vein endothelial cell line ECV304 in vitro. The expression of CXCR4 in ECV304 cells is notably down-regulated after TMP treatment. In addition, TMP significantly suppresses corneal neovascularization in a rat model of corneal alkali burn injury. The expression of CXCR4 on days 1, 3 and 7 post-injury was determined through RT-PCR analysis. Consistent with our hypotheses, the expression of CXCR4 in the rat cornea is significantly increased with alkali burn and dramatically down-regulated with TMP treatment. Moreover, TMP treatment significantly attenuates bleomycin-induced rat pulmonary fibrosis, while immunofluorescence shows a notably decreased amount of CXCR4-positive cells in the TMP-treated group. Furthermore, TMP significantly down-regulates the expression of CXCR4 in platelets, lymphocytes and red blood cells. Whole-blood viscosity and platelet aggregation in rats are significantly decreased by TMP treatment.<h4>Conclusions</h4>These results show that TMP exerts potent effects in inhibiting neovascularization, fibrosis and thrombosis under pathological conditions; thus, the underlying mechanism of TMP might partially contribute to the down-regulation of CXCR4.
format	article
author	Xiaoxiao Cai Zhao Chen Xueke Pan Lei Xia Pei Chen Ying Yang Huan Hu Jing Zhang Kaijing Li Jian Ge Keming Yu Jing Zhuang
author_facet	Xiaoxiao Cai Zhao Chen Xueke Pan Lei Xia Pei Chen Ying Yang Huan Hu Jing Zhang Kaijing Li Jian Ge Keming Yu Jing Zhuang
author_sort	Xiaoxiao Cai
title	Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.
title_short	Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.
title_full	Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.
title_fullStr	Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.
title_full_unstemmed	Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.
title_sort	inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the sdf-1/cxcr4 axis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/8fb29db02ea342ccbf0a52cd4278e556
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Inhibition of angiogenesis, fibrosis and thrombosis by tetramethylpyrazine: mechanisms contributing to the SDF-1/CXCR4 axis.

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