@article{5262efc2ae254e90a6f83eae1a1e89c7,
title = "Ginsenoside Rb1 prevents homocysteine-induced EPC dysfunction via VEGF/p38MAPK and SDF-1/CXCR4 activation",
abstract = "Hyperhomocystinemia (HHcy) is known as an independent risk factor for cardiovascular disease. Our previous study showed that ginsenoside Rb1, the major active constituent of ginseng, prevents homocysteine (Hcy)-induced endothelial damage. However, the role of ginsenoside Rb1 in Hcy-induced dysfunction in endothelial progenitor cells (EPCs) remains unknown. In the study, we found that ginsenoside Rb1 reversed the Hcy-induced impairment of adhesive and migratory ability in EPCs which were significantly abolished by CXCR4 antagonist AMD3100 and VEGFR2 inhibitor SU5416. Ginsenoside Rb1 significantly reversed Hcy-induced SDF-1 reduction in the supernatant and in the serum. Ginsenoside Rb1 reversed downregulation of SDF-1 and VEGFR2 protein expression, inhibition of p38MAPK phosphorylation induced by Hcy. Re-endothelialization in balloon-injured carotid arteries significantly increased with EPCs transplant, and was even better with Rb1 treatment. This effect was significantly abolished by AMD3100. AMD3100 also decreased the number of CM-DiI labeled EPCs in injured arteries. Here we show for the first time that Rb1 prevents Hcy-induced EPC dysfunction via VEGF/p38MAPK and SDF-1/CXCR4 activation. These findings demonstrate a novel mechanism of the action of Rb1 that may have value in prevention of HHcy associated cardiovascular disease.",
author = "Lan, {Tao Hua} and Xu, {Dan Ping} and Huang, {Man Ting} and Juxian SONG and Wu, {Huan Lin} and Min LI",
note = "Funding Information: The present work was supported by National Natural Science Foundation of China (Grant No. 81202815 and 81403341), General Financial Grant from the China Postdoctoral Science Foundation (Grant No. 2012M511787), and The Hong Kong Scholars Program, RGC/HKBU-121009/14, HMRF 12132091 from Hong Kong Government. Funding Information: Reagents and antibodies. Ginsenoside Rb1(Rb1) purchased as a reference compound (purity > 98%) from the Division of Chinese Materia Medica and Natural Products, National Institute for the Control of Pharmaceutical and Biological Products (NICPBP), Ministry of Public Health, China. EGM-2MV was purchased from Lonza (Switzerland). DiI-ac-LDL was purchased from Molecular Probe (Thermo Scientific, Waltham, MA, USA). Antibodies against Flk-1, CD133 and CD34 were purchased from Bioss (Beijing, China). Trypsin, penicillin, streptomycin, CM-DiI and FBS were purchased from Gibco (Invitrogen, Carlsbad, CA, USA). Fibronetin was purchased from BD Biosciences (San Jose, CA, USA). L-methionine, SST, FITC-UEA, Hcy, Ficoll, H2DCF-DA, DAPI, Evans blue, AMD3100, SU5416 and GAPDH antibody were purchased from Sigma (St Louis, MO, USA). SDF-1 ELISA Kit was purchased from Cusabio (Wuhan, China). Antibodies against p38MAPK, phosphor-p38MAPK, SDF-1, VEGFR2 and tubulin were purchased from Cell Signaling Technology (Boston, MASS, USA). Fogarty catheter was purchased from Edwards Lifesciences (Irvine, CA, USA).",
year = "2017",
month = dec,
day = "1",
doi = "10.1038/s41598-017-13436-7",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}
