Rehmannia glutinosa extract activates endothelial progenitor cells in a rat model of myocardial infarction through a SDF-1 α/CXCR4 cascade.
OBJECTIVE
Endothelial progenitor cells (EPCs) can be used to repair tissues after myocardial infarction (MI) but EPC activators have adverse reactions. Rehmannia glutinosa is a herb used in traditional Chinese medicine, which can promote bone-marrow proliferation and protect the ischemic myocardium. We investigated the effects of Rehmannia glutinosa extract (RGE) on EPCs in a rat model of MI.


METHODS
A total of 120 male Wistar rats were randomized to 2 groups (n=60 each) for treatment: high-dose RGE (1.5 g·kg(-1)·day(-1) orally) for 8 weeks, then left anterior descending coronary artery ligation, mock surgery or no treatment, then RGE orally for 4 weeks; or normal saline (NS) as the above protocol. The infarct region of the left ventricle was assessed by serial sectioning and morphology. EPCs were evaluated by number and function. Protein and mRNA levels of CD133, vascular endothelial growth factor receptor 2 (VEGFR2), chemokine C-X-C motif receptor 4 (CXCR4), stromal cell-derived factor-1α (SDF-1α) were measured by immunohistochemistry, Western blot and quantitative PCR analysis.


RESULTS
RGE significantly improved left ventricular function, decreased the ischemic area and the apoptotic index in the infarct myocardium, also decreased the concentration of serum cardiac troponin T and brain natriuretic peptide at the chronic stage after MI (from week 2 to week 4). RGE increased EPC number, proliferation, migration and tube-formation capacity. It was able to up-regulate the expression of angiogenesis-associated ligand/receptor, including CD133, VEGFR2 and SDF-1α/CXCR4. In vitro, the effect of RGE on SDF-1α/CXCR4 cascade was reversed by the CXCR4 specific antagonist AMD3100.


CONCLUSIONS
RGE may enhance the mobilization, migration and therapeutic angiogenesis of EPCs after MI by activating the SDF-1α/CXCR4 cascade.
Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University, Jinan, Shandong, China.
Ying-Bin
YB
Wang
Yun-Fang
YF
Liu
Xiao-Ting
XT
Lu
Fang-Fang
FF
Yan
Bo
B
Wang
Wen-Wu
WW
Bai
Yu-Xia
YX
Zhao
D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D032267:Rehmannia / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D006023:Glycoproteins; D010455:Peptides; D010936:Plant Extracts; C000606025:Prom1 protein, rat; D019718:Receptors, CXCR4; D040301:Vascular Endothelial Growth Factor Receptor-2