scholarly journals Suppression of oxidative stress in endothelial progenitor cells promotes angiogenesis and improves cardiac function following myocardial infarction in diabetic mice

2016 ◽  
Vol 11 (6) ◽  
pp. 2163-2170 ◽  
Author(s):  
PENG JIN ◽  
TAO LI ◽  
XUEQI LI ◽  
XINGHUA SHEN ◽  
YANRU ZHAO
Keyword(s):  
Oxidative Stress ◽  
Myocardial Infarction ◽  
Cardiac Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Diabetic Mice ◽  
Endothelial Progenitor

scholarly journals Endothelial overexpression of metallothionein prevents diabetes mellitus-induced impairment in ischemia angiogenesis via preservation of HIF-1α/SDF-1/VEGF signaling in endothelial progenitor cells

2020 ◽  
Author(s):  
Ada Admin ◽  
Kai Wang ◽  
Xiaozhen Dai ◽  
Junhong He ◽  
Xiaoqing Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Flow ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mononuclear Cells ◽  
Tube Formation ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Endothelial Progenitor ◽  
Vegf Signaling

Diabetes-induced oxidative stress is one of the major contributors to dysfunction of endothelial progenitor cells (EPCs) and impaired endothelial regeneration. Thus, we tested whether increasing antioxidant protein metallothionein (MT) in EPCs promotes angiogenesis in a hind limb ischemia (HLI) model in endothelial MT transgenic (JTMT) mice with high fat diet and streptozocin-induced diabetes. Compared with littermate wild-type (WT) diabetic mice, JTMT diabetic mice had improved blood flow recovery and angiogenesis after HLI. Similarly, transplantation of JTMT bone marrow-derived mononuclear cells (BM-MNCs) stimulated greater blood flow recovery in <i>db/db</i> mice with HLI than did WT BM-MNCs. The improved recovery was associated with augmented EPC mobilization and angiogenic function. Further, cultured EPCs from diabetic patients exhibited decreased MT expression, increased cell apoptosis and impaired tube formation; while cultured JTMT-EPCs had enhanced cell survival, migration, and tube formation in hypoxia/hyperglycemic conditions compared with WT-EPCs. Mechanistically, MT overexpression enhanced hypoxia-inducible factor 1α (HIF-1α), stromal cell-derived factor (SDF-1) and vascular endothelial growth factor (VEGF) expression, and reduced oxidative stress in ischemic tissues. MT’s pro-EPC effects were abrogated by siRNA knockdown of HIF-1α without affecting MT’s anti-oxidant action. These results indicate that endothelial MT overexpression is sufficient to protect against diabetes-induced impairment of angiogenesis by promoting EPC functions most likely through upregulation of HIF-1α/SDF-1/VEGF signaling and reducing oxidative stress.

scholarly journals Endothelial overexpression of metallothionein prevents diabetes mellitus-induced impairment in ischemia angiogenesis via preservation of HIF-1α/SDF-1/VEGF signaling in endothelial progenitor cells

2020 ◽  
Author(s):  
Ada Admin ◽  
Kai Wang ◽  
Xiaozhen Dai ◽  
Junhong He ◽  
Xiaoqing Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Flow ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Mononuclear Cells ◽  
Tube Formation ◽  
Diabetic Patients ◽  
Diabetic Mice ◽  
Endothelial Progenitor ◽  
Vegf Signaling

Diabetes-induced oxidative stress is one of the major contributors to dysfunction of endothelial progenitor cells (EPCs) and impaired endothelial regeneration. Thus, we tested whether increasing antioxidant protein metallothionein (MT) in EPCs promotes angiogenesis in a hind limb ischemia (HLI) model in endothelial MT transgenic (JTMT) mice with high fat diet and streptozocin-induced diabetes. Compared with littermate wild-type (WT) diabetic mice, JTMT diabetic mice had improved blood flow recovery and angiogenesis after HLI. Similarly, transplantation of JTMT bone marrow-derived mononuclear cells (BM-MNCs) stimulated greater blood flow recovery in <i>db/db</i> mice with HLI than did WT BM-MNCs. The improved recovery was associated with augmented EPC mobilization and angiogenic function. Further, cultured EPCs from diabetic patients exhibited decreased MT expression, increased cell apoptosis and impaired tube formation; while cultured JTMT-EPCs had enhanced cell survival, migration, and tube formation in hypoxia/hyperglycemic conditions compared with WT-EPCs. Mechanistically, MT overexpression enhanced hypoxia-inducible factor 1α (HIF-1α), stromal cell-derived factor (SDF-1) and vascular endothelial growth factor (VEGF) expression, and reduced oxidative stress in ischemic tissues. MT’s pro-EPC effects were abrogated by siRNA knockdown of HIF-1α without affecting MT’s anti-oxidant action. These results indicate that endothelial MT overexpression is sufficient to protect against diabetes-induced impairment of angiogenesis by promoting EPC functions most likely through upregulation of HIF-1α/SDF-1/VEGF signaling and reducing oxidative stress.

Abstract 13054: Thymosin Beta-4-Treated Endothelial Progenitor Cells Improve Cardiac Function and Vasculogenesis in Diabetic Obese Rats with Myocardial Infarction

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Poay Sian S Lee ◽  
Lei Ye ◽  
Yei-Tsung Chen ◽  
Eric Yin Hao Khoo ◽  
Tiong Cheng Yeo ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Left Ventricular ◽  
Mrna Levels ◽  
Endothelial Progenitor ◽  
Thymosin Beta 4 ◽  
Zdf Rats ◽  
Angiogenic Cytokines

Introduction: Diabetes and obesity are associated with endothelial dysfunction and may impair circulating endothelial progenitor cells (EPCs). Thymosin beta-4 (Tβ4), a novel peptide with angiogenic properties, may improve EPC number and function. Hypothesis: We aim to transplant allogenic Tβ4-treated EPCs in Zucker Diabetic Fatty (ZDF) rats with myocardial infarction (MI) and hypothesize that Tβ4-treated EPCs may improve cardiac function, vasculogenesis and upregulate angiogenic cytokines and genes, compared to non-treated EPCs and controls. Methods: The left anterior descending coronary artery was permanently ligated to induce experimental MI on ZDF rats (n=19), divided into MI+saline(n=6); MI+EPCs (n=6) and MI+Tβ4-treated EPCs (n=7). Peripheral blood mononuclear cells were harvested from ZDF rats and isolated using Ficoll density gradient centrifugation and grown on fibronectin-coated plates. EPCs were treated with Tβ4 (1μg/mL) on day 7. At day 10, allogenic EPCs were harvested and transplanted into the peri-infarcted myocardium. Echocardiographic examination including strain assessment, immunohistological assessments and assays of angiogenic cytokines were performed 6 weeks after surgery. Results: Left ventricular (LV) ejection fraction was improved in Tβ4-treated EPCs (72.0±7.6%) and non-treated EPCs rats (80.5±5.9%) compared to control MI rats (64.8±19.7%) (P=0.04). Similar improvement was observed in LV radial strain rate in rats with Tβ4-treated EPCs (-7.22±1.24 1/s) and non-treated EPCs (-6.67±2.66 1/s) compared to MI only (-4.08±3.75 1/s) (P<0.01). Vascular density (CD31) and c-kit density (CD117) were significantly upregulated in Tβ4-treated EPCs rats compared to MI (P=0.03; P=0.005 respectively) and non-treated EPCs rats (P=0.04; P=0.04 respectively). Angiogenic cytokines of PDGF-BB, IGF-1 and VEGF levels were increased by 1.5 fold in Tβ4-treated EPCs and supported by similar trend in mRNA levels compared to non-treated EPCs (P<0.01). Conclusions: ZDF rats with Tβ4-treated EPCs had significant improvement in cardiac function, increased vasculogenesis and upregulation of angiogenic cytokines and genes. This suggests that Tβ4 may be beneficial in enhancing efficacy of EPCs in cell-based therapies.

Impaired development and dysfunction of endothelial progenitor cells in type 2 diabetic mice

2017 ◽  
Vol 43 (2) ◽  
pp. 154-162 ◽  
Author(s):  
S. Tsukada ◽  
H. Masuda ◽  
S.Y. Jung ◽  
J. Yun ◽  
S. Kang ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Diabetic Mice ◽  
Endothelial Progenitor ◽  
Type 2 Diabetic
Sign in / Sign up

Export Citation Format

Share Document