scholarly journals Angiogenic Factor AGGF1-Primed Endothelial Progenitor Cells Repair Vascular Defect in Diabetic Mice

Diabetes ◽  
2019 ◽  
pp. db181178 ◽  
Author(s):  
Yufeng Yao ◽  
Yong Li ◽  
Qixue Song ◽  
Changqin Hu ◽  
Wen Xie ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Angiogenic Factor ◽  
Diabetic Mice ◽  
Endothelial Progenitor ◽  
Vascular Defect

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

scholarly journals Integrins α4β1 and αVβ3 are Reduced in Endothelial Progenitor Cells from Diabetic Dyslipidemic Mice and May Represent New Targets for Therapy in Aortic Valve Disease

2020 ◽  
Vol 29 ◽  
pp. 096368972094627
Author(s):  
Alexandru Filippi ◽  
Alina Constantin ◽  
Nicoleta Alexandru ◽  
Geanina Voicu ◽  
Cristina Ana Constantinescu ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Chemokine Receptor ◽  
Atherogenic Diet ◽  
Diabetic Mice ◽  
Aortic Valves ◽  
Endothelial Progenitor ◽  
Citrate Buffer ◽  
Early Diabetes

Diabetes reduces the number and induces dysfunction in circulating endothelial progenitor cells (EPCs) by mechanisms that are still uncovered. This study aims to evaluate the number, viability, phenotype, and function of EPCs in dyslipidemic mice with early diabetes mellitus and EPC infiltration in the aortic valve in order to identify possible therapeutic targets in diabetes-associated cardiovascular disease. A streptozotocin-induced diabetic apolipoprotein E knock-out (ApoE−/−) mouse model was used to identify the early and progressive changes, at 4 or 7 days on atherogenic diet after the last streptozotocin or citrate buffer injection. Blood and aortic valves from diabetic or nondiabetic ApoE−/− animals were collected. EPCs were identified as CD34 and vascular endothelial growth factor receptor 2 positive monocytes, and the expression levels of α4β1, αVβ3, αVβ5, β1, αLβ2, α5 integrins, and C-X-C chemokine receptor type 4 chemokine receptor on EPC surface were assessed by flow cytometry. The number of CD34 positive cells in the aortic valve, previously found to be recruited progenitor cells, was measured by fluorescence microscopy. Our results show that aortic valves from mice fed 7 days with atherogenic diet presented a significantly higher number of CD34 positive cells compared with mice fed only 4 days with the same diet, and diabetes reversed this finding. We also show a reduction of circulatory EPC numbers in diabetic mice caused by cell senescence and lower mobilization. Dyslipidemia induced EPC death through apoptosis regardless of the presence of diabetes, as shown by the higher percent of propidium iodide positive cells and higher cleaved caspase-3 levels. EPCs from diabetic mice expressed α4β1 and αVβ3 integrins at a lower level, while the rest of the integrins tested were unaffected by diabetes or diet. In conclusion, reduced EPC number and expression of α4β1 and αVβ3 integrins on EPCs at 4 and 7 days after diabetes induction in atherosclerosis-prone mice have resulted in lower recruitment of EPCs in the aortic valve.

Moderate intake of red wine improves ischemia-induced neovascularization in diabetic mice—Roles of endothelial progenitor cells and nitric oxide

2010 ◽  
Vol 212 (2) ◽  
pp. 426-435 ◽  
Author(s):  
Po-Hsun Huang ◽  
Hsiao-Ya Tsai ◽  
Chao-Hung Wang ◽  
Yung-Hsiang Chen ◽  
Jia-Shiong Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Red Wine ◽  
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.

Abstract 019: Diabetic Endothelial Progenitor Cells in Combination with an RGDS Presenting Peptide Amphiphile Enhance Recovery from Critical Limb Ischemia in Diabetic Mice

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Erin E Vaughan ◽  
Eduard Sleep ◽  
Sol Misener ◽  
Aiko Ito Klinger ◽  
Veronica Ramirez ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Critical Limb Ischemia ◽  
Limb Ischemia ◽  
Laser Doppler ◽  
Diabetic Mice ◽  
Endothelial Progenitor ◽  
Peptide Amphiphile ◽  
Post Surgery ◽  
The Impact

Approximately two million people suffer from critical limb ischemia (CLI) with the prevalence of the disease expected to rise. Thus, there is a crucial need to develop new therapies to enhance angiogenesis and minimize the impact of the blocked vessel(s). Cell therapy using endothelial progenitor cells (EPCs) has shown some promise, however, the cells may not remain at the site of injury long enough to significantly impact the course of the disease. Further, the use of autologous cells may be problematic as the underlying disease, such as diabetes, which resulted in CLI also appears to negatively impact the function of EPCs. Thus, we propose to use a biomaterial in combination with the EPCs to enhance both the retention of cells at the site of injury and also enhance the function of the cells. A self-assembling peptide amphiphile (PA) was developed with an attached functional group consisting of the cell-attachment sequence of peptides identified in fibronectin: RGDS. We hypothesize that EPCs combined with RGDS PA will improve the angiogenic response in CLI. Indeed, in vitro we found that EPCs from diabetic mice (db/db) exhibited increased survival on an RGDS PA in comparison to a scrambled sequence (DGRS) PA as measured by calcein-AM and ethidium homodimer-1 staining. To test if this enhanced survival would improve critical limb ischemia in diabetic mice, uni-lateral ischemia was induced by ligation of the femoral artery. Three days post surgery ischemia was confirmed by laser Doppler and the following treatments were injected into the ischemic limb of the diabetic mice: (1) PBS (2) scrambled PA (3) RGDS (4) scrambled PA +100,000 diabetic EPCs (5) RGDS PA + 100,000 diabetic EPCs. At four weeks post-injection, blood flow (as measured by laser Doppler) was increased in the group receiving RGDS PA when compared to the other groups (n>6). Further, necrosis was decreased in the RGDS PA group and muscle regeneration, as measured by the number of central nuclei, was increased in the RGDS PA group. Taken together, these results suggest that RGDS PA in combination with db/db EPCs enhances recovery from CLI in diabetic mice.

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