Carbon dioxyde-rich water bathing enhances collatéral blood flow in ischémie hindlimb via mobilization of endothelial progenitor cells and activation of NO-cGMP System

Abstract Background Arterial atherosclerotic occlusive syndrome remains the leading cause of mortality and morbidity worldwide. Peripheral arterial occlusive disease (PAOD) is a manifestation of atherosclerosis in the lower extremities. In our previous preclinical study, hyperbaric oxygen (HBO) therapy improved ischemic PAOD mainly through an increase of vascular wall permeability and recruiting endothelial progenitor cells (EPCs) to enhance the angiogenesis and blood flow in the ischemic area. Purpose This study tested the hypothesis that hyperbaric oxygen (HBO) therapy enhanced the circulating levels of endothelial progenitor cells (EPCs), soluble angiogenesis factors and blood flow in ischemic area in patients with peripheral arterial occlusive disease (PAOD). Methods 57 consecutive patients with PAOD undergoing the HBO therapy (3 atm for 2h/each time) were prospectively enrolled into the present study. The venous blood sampling was drawn for assessing the circulating levels of EPCs and soluble angiogenesis factors prior to and during five times of HBO therapy. Additionally, skin perfusion pressure (SPP), an indicator of blood flow at ischemic area, was measured by moorVMS-PRES. Results The results demonstrated that the circulating levels of EPCs (CD34+/CD133+/CD45dim, CD31+/CD133+/CD45dim, CD34+) and soluble angiogenesis factors (VEGF/SDF-1α/HGF/FGF) were significantly increased in post-HBO therapy than in pre-HBO therapy (all p<0.01). Additionally, Matrigel assay exhibited that the angiogenesis was significantly increased in post-HBO therapy than prior to the therapy (p<0.001). Furthermore, the SPP was significantly increased in ischemic area (i.e., plantar foot and mean SPP of the ischemic foot) in post-HBO therapy than in pre-HBO therapy (all p<0.01). Importantly, the HBO therapy did not show any complication and all the patients were uneventfully discharged without amputation. Conclusions HBO therapy augmented circulating levels of EPCs and angiogenesis factors as well as improved the blood flow in the ischemic area. Acknowledgement/Funding Kaohsiung Chang Gung Memorial Hospital, Taiwan Society of Stem Cell Research

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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

10.2337/figshare.12280736 ◽

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.

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Chronic hyperuricemia impairs blood flow recovery in the ischemic hindlimb through suppression of endothelial progenitor cells

Oncotarget ◽

10.18632/oncotarget.24290 ◽

2018 ◽

Vol 9 (10) ◽

pp. 9285-9298 ◽

Cited By ~ 4

Author(s):

I-Chun Chen ◽

Chin-Sung Kuo ◽

Chih-Cheng Wu ◽

Hsiao-Ya Tsai ◽

Chih-Pei Lin ◽

...

Keyword(s):

Blood Flow ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Endothelial Progenitor

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The Impact of Maternal Fructose Exposure on Angiogenic Activity of Endothelial Progenitor Cells and Blood Flow Recovery After Critical Limb Ischemia in Rat Offspring

International Journal of Molecular Sciences ◽

10.3390/ijms20102429 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2429 ◽

Cited By ~ 1

Author(s):

Steve Leu ◽

Kay L. H. Wu ◽

Wei-Chia Lee ◽

You-Lin Tain ◽

Julie Y. H. Chan

Keyword(s):

Blood Flow ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Critical Limb Ischemia ◽

Limb Ischemia ◽

Cellular Migration ◽

Endothelial Progenitor ◽

Western Blots ◽

Angiogenic Activity ◽

The Impact

Adult metabolic syndrome is considered to be elicited by the developmental programming which is regulated by the prenatal environment. The maternal excess intake of fructose, a wildly used food additive, is found to be associated with developmental programing-associated cardiovascular diseases. To investigate the effect of maternal fructose exposure (MFE) on endothelial function and repair, which participate in the initiation and progress of cardiovascular disease, we applied a rat model with maternal fructose excess intake during gestational and lactational stage and examined the number and function of endothelial progenitor cells (EPCs) in 3-month-old male offspring with induction of critical limb ischemia (CLI). Results showed that the circulating levels of c-Kit+/CD31+ and Sca-1+/KDR+ EPC were reduced by MFE. In vitro angiogenesis analysis indicated the angiogenic activity of bone marrow-derived EPC, including tube formation and cellular migration, was reduced by MFE. Western blots further indicated the phosphorylated levels of ERK1/2, p38-MAPK, and JNK in circulating peripheral blood mononuclear cells were up-regulated by MFE. Fourteen days after CLI, the reduced blood flow recovery, lowered capillary density, and increased fibrotic area in quadriceps were observed in offspring with MFE. Moreover, the aortic endothelium-mediated vasorelaxant response in offspring was impaired by MFE. In conclusion, maternal fructose intake during gestational and lactational stage modulates the number and angiogenic activity of EPCs and results in poor blood flow recovery after ischemic injury.

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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

10.2337/figshare.12280736.v1 ◽

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.

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