Abstract
Ginsenoside-Rg1 (Rg1) has been used in the traditional Chinese medicine for over 2,000 years. The present study was performed to test our hypothesis that Rg1 provides pro-angiogenic and anti-fibrotic benefits in the ischemic myocardium in a rat model of myocardial infarction. The expression of vascular endothelial growth factor (VEGF) and phosphorylation/activation of PI3K, Akt, and p38 MAPK signaling pathways were examined in human umbilical vein endothelial cells and in the myocardial samples of rats. In addition, the expression levels of TNF-α and collagen I level, the number of newly formed blood vessels, the extent of myocardial fibrosis, and left ventricular function were measured in vivo. Our results demonstrated that administration of Rg1 increased VEGF expression levels, activated PI3K/Akt, and inhibited p38 MAPK in vitro and in vivo. Furthermore, Rg1 increased the density of newly formed vessels, decreased TNF-α and collagen I expression levels and area of myocardial fibrosis, and improved left ventricle function in vivo. PI3K inhibitor LY294002 significantly attenuated Rg1-enhanced VEGF expression and capillary density. As well, inhibition of p38 MAPK slightly increased VEGF expression in vitro and in vivo, increased capillary density, and decreased TNF-α and collagen I expression levels and area of myocardial fibrosis in vivo. Rg1-induced activation of PI3K/Akt also contributed to the downregulation of p38 MAPK. Thus, Rg1 is effective in promoting angiogenesis and attenuating myocardial fibrosis, resulting in ameliorated left ventricular function. The possible mechanisms may involve activation of PI3K/Akt, inhibition of p38 MAPK, and cross talk between the two signaling pathways.
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Acknowledgment
This work was supported by the National 973 Basic Research Program of China (no. 2010CB732605). the National High-tech Research and Development Program of China (no. 2006AA02A406), the State Program of National Natural Science Foundation of China for Innovative Research Group (81021001), the State Key Program of National Natural Science of China (no. 60831003), the National Natural Science Foundation of China (nos. 30700301, 30971096, and 30972809), the Major Project of Fujian Medical University (09ZD019), the Foundation for Excellent Young Scientists of Shandong Province (BS2009SW026, 2008BS03017), and the Natural Science Foundation of Shandong Province (ZR2010HQ012, ZR2009CZ003, and Q2006C12).
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This article has been retracted upon request of the authors. The retraction has been made due to duplication of blots in Figure 1a and Figure 3 in this paper. The authors deeply apologize for any inconvenience this may have caused to the readers.
The retraction note to this article can be found online at http://dx.doi.org/10.1007/s00109-013-1018-0.
Huiqiu Yin and Zhaoqiang Liu contributed equally to this work.
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Yin, H., Liu, Z., Li, F. et al. RETRACTED ARTICLE: Ginsenoside-Rg1 enhances angiogenesis and ameliorates ventricular remodeling in a rat model of myocardial infarction. J Mol Med 89, 363–375 (2011). https://doi.org/10.1007/s00109-011-0723-9
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DOI: https://doi.org/10.1007/s00109-011-0723-9