Influence of HMGB1 and MSCs transplantation on rat cardiac angiogenesis with acute myocardial infarction.
To observe whether HMGB1could enhance the paracrine effect of MSCs when the Mesenchymal stem cells (Mesenchymal stem cells, MSCs) are pre-proccessed by High Mobility Group Box-1 (High Mobility Group Box-1, HMGB1). And to observe whether it can further increase the quantity of local angiogenesis in myocardial infarcts on the rat model with acute myocardial infarction, HMGB1 was combined with MSCs transplantation. MSCs in rats were cultivated with adherence and centrifugation method. Receptors of TLR4and RAGE in HMGB1 were tested. The MSCs were interfered by HMGB1 with different concentration gradient respectively, then the expression of VEGF was tested with ELISA method. SD male rats were divided into four groups: the model group, the MSCs transplantation group, the HMGB1 injection group, the HMGB1 injection plus MSCs transplantation group (n = 24), preparing rat model with acute myocardial infarction. The serum VEGF concentration levels were detected on the 3rd day, 7th and 28th day with ELISA method. On the 28th day after post operation the density of angiogenesis in infarction area was detected by immunohistochemal. (1) MSCs owned the expression of TLR4 and RAGE. (2) the secretion of VEGF increased significantly after the intervention of HMGB1 with concentration of 12.5 ng/mL, 25 ng/mL, 50 ng/mL, 100 ng/mL and 200ng/ml on MSCs compared with the control group. While the concentration was 400ng/ml or 800ng/ml, the secretion of VEGF decreased compared with the control group (P < 0.05). (3) detection of the serum VEGF on the 3rd or7th day after post operation was arranged: The results showed that: HMGB1 injection plus MSCs transplantation group > MSCs transplantation group >HMGB1 injection group >model group (P < 0.05). (4) the quantity of CD31 stained angiogenesis in HMGB1 injection plus MSCs transplantation group increased obviously. Combining MSCs transplantation, contributed to new angiogenesis of rats with acute myocardial infarction in myocardial infarction area and its near area in rats with acute myocardial infarction.
Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Youxu
Y
Jiang
Department of Emergency, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Xiaoman
X
Wang
Department of Anatomy, Zhengzhou Health School, Zhengzhou, China.
Xiaodong
X
Jiang
Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Shaohui
S
Niu
Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Lihua
L
Zhang
D000818:Animals; D002470:Cell Survival; D004562:Electrocardiography; D024243:HMGB1 Protein / Q000494:pharmacology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products / Q000096:biosynthesis / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C000593874:Ager protein, rat; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000067759:Receptor for Advanced Glycation End Products; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat