Zhen Hu1, Hong Wang2, Guanwei Fan3, Han Zhang2, Xiaoying Wang2, Jingyuan Mao4, Yingqiang Zhao5, Yi An6, Yuhong Huang5, Chuan Li7, Lianying Chang4, Xianming Chu6, Yanfen Li5, Yuan Zhang8, Gangjian Qin9, Xiumei Gao10, Boli Zhang2. 1. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 Anshan West Road, Tianjin 300193, China; Tianjin State Key Laboratory of Modern Chinese Medicine and key research department of prescription component compatibility, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China; Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China. 2. Tianjin State Key Laboratory of Modern Chinese Medicine and key research department of prescription component compatibility, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China; Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China. 3. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 Anshan West Road, Tianjin 300193, China; Tianjin State Key Laboratory of Modern Chinese Medicine and key research department of prescription component compatibility, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China; Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China. Electronic address: fgw1005@hotmail.com. 4. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 314 Anshan West Road, Tianjin 300193, China. 5. Second Teaching Hospital of Tianjin University of Traditional Chinese Medicine, 816 Zhenli Road, Tianjin 300150, China. 6. The affiliated cardiovascular hospital of Qingdao university, 5 Zhiquan Road, Qingdao 266071, China. 7. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China. 8. Tianjin State Key Laboratory of Modern Chinese Medicine and key research department of prescription component compatibility, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China. 9. Tianjin State Key Laboratory of Modern Chinese Medicine and key research department of prescription component compatibility, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China; Department of Biomedical Engineering, School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, Alabama, USA. 10. Tianjin State Key Laboratory of Modern Chinese Medicine and key research department of prescription component compatibility, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China; Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae, Ministry of Education, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China. Electronic address: gaoxiumei@tjutcm.edu.cn.
Abstract
BACKGROUD: Endothelial progenitor cells (EPCs) have been characterized as one of the key effectors of endothelial healing. The effect of Danhong injection (DHI), the most widely prescribed Chinese medicine for coronary heart disease (CHD), on EPCs mobilization remains unclear. PURPOSE: We aimed to assess the effect of DHI on EPCs mobilization to repair percutaneous coronary intervention (PCI) induced vascular injury, and to investigate the characteristics and potential mechanism of DHI on EPCs mobilization. METHOD: Forty-two patients with CHD underwent PCI and received stent implantation were enrolled in a Phase II clinical trials. All patients received routine western medical treatment after PCI, patients of DHI group received DHI in addition. The levels of CECs, cytokines (vWF, IL-6, CRP) and EPCs were analyzed at baseline, post-PCI and after treatment. To investigate the characteristics of DHI on EPCs mobilization, 12 healthy volunteers received intravenous infusion of DHI once and the other 12 received for 7 days. EPCs enumeration were done at a series of time points. At last we tested the effect of DHI and three chemical constituents of DHI (danshensu; lithospermic acid, LA; salvianolic acid D, SaD) on EPCs level and expression of Akt, eNOS and MMP-9 in bone marrow cells of myocardial infarction (MI) mice. RESULTS: In the DHI group the angina symptoms were improved, the levels of cytokines and CECs were reduced; while EPCs population was increased after treatment. In the phase I clinical trials, EPCs counts reached a plateau phase in 9 h and maintained for more than 10 h after a single dose. After continuous administration, EPCs levels plateaued on the 3rd or 4th day, and maintain till 1 day after the withdrawal, then its levels gradually declined. DHI treatment induced a timely dependent mobilization of EPCs. DHI promoted EPCs mobilization via upregulating the expression of Akt, eNOS and MMP-9 in BM. LA and SaD have played a valuable role in EPCs mobilization. CONCLUSION: These initial results demonstrated that DHI is effective in alleviating endothelial injury and promoting endothelial repair through enhancing EPCs mobilization and revealed the effect feature and possible mechanisms of DHI in mobilizing EPCs.
BACKGROUD: Endothelial progenitor cells (EPCs) have been characterized as one of the key effectors of endothelial healing. The effect of Danhong injection (DHI), the most widely prescribed Chinese medicine for coronary heart disease (CHD), on EPCs mobilization remains unclear. PURPOSE: We aimed to assess the effect of DHI on EPCs mobilization to repair percutaneous coronary intervention (PCI) induced vascular injury, and to investigate the characteristics and potential mechanism of DHI on EPCs mobilization. METHOD: Forty-two patients with CHD underwent PCI and received stent implantation were enrolled in a Phase II clinical trials. All patients received routine western medical treatment after PCI, patients of DHI group received DHI in addition. The levels of CECs, cytokines (vWF, IL-6, CRP) and EPCs were analyzed at baseline, post-PCI and after treatment. To investigate the characteristics of DHI on EPCs mobilization, 12 healthy volunteers received intravenous infusion of DHI once and the other 12 received for 7 days. EPCs enumeration were done at a series of time points. At last we tested the effect of DHI and three chemical constituents of DHI (danshensu; lithospermic acid, LA; salvianolic acid D, SaD) on EPCs level and expression of Akt, eNOS and MMP-9 in bone marrow cells of myocardial infarction (MI) mice. RESULTS: In the DHI group the angina symptoms were improved, the levels of cytokines and CECs were reduced; while EPCs population was increased after treatment. In the phase I clinical trials, EPCs counts reached a plateau phase in 9 h and maintained for more than 10 h after a single dose. After continuous administration, EPCs levels plateaued on the 3rd or 4th day, and maintain till 1 day after the withdrawal, then its levels gradually declined. DHI treatment induced a timely dependent mobilization of EPCs. DHI promoted EPCs mobilization via upregulating the expression of Akt, eNOS and MMP-9 in BM. LA and SaD have played a valuable role in EPCs mobilization. CONCLUSION: These initial results demonstrated that DHI is effective in alleviating endothelial injury and promoting endothelial repair through enhancing EPCs mobilization and revealed the effect feature and possible mechanisms of DHI in mobilizing EPCs.