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

Po Hsun Huang, Hsiao Ya Tsai, Chao Hung Wang, Yung Hsiang Chen, Jia Shiong Chen, Feng Yen Lin, Chih Pei Lin, Tao Cheng Wu, Masataka Sata, Jaw Wen Chen, Shing Jong Lin

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Abstract

Objective: Circulating endothelial progenitor cells (EPCs) play a significant role in postnatal neovascularization. Patients with diabetes have attenuated EPC functions and impaired angiogenic response after tissue ischemia. We investigated whether moderate red wine consumption can enhance blood flow recovery in response to tissue ischemia by enhancement of EPC functions in diabetic mice. Methods and results: Starting at 4 weeks after diabetes onset, red wine (4ml/kg/day) or ethanol were administered to streptozotocin (STZ)-induced (type 1) diabetic mice and KKAy-Ta (type 2) mice. Unilateral hind limb ischemia surgery was conducted after 2 weeks of red wine or ethanol ingestion. Type 1 and type 2 diabetic mice given red wine, but not ethanol, had significantly increased collateral flow about 30% and augmented capillary density in ischemic tissues. These beneficial effects were markedly abolished by an eNOS inhibitor (L-NAME). Flow cytometry analysis showed impaired EPC-like cells (Sca-1+/Flk-1+) mobilization after ischemia surgery in diabetic mice, but augmented mobilization in red wine group (baseline vs. 2 days after operation: 0.88±0.06% vs. 1.73±0.29%, p=0.010). C-kit positive bone marrow cells isolated from diabetic mice given red wine had enhanced adhesion and migration compared to mice given vehicle. By in-vitro studies, incubation with red wine in high-glucose medium significantly reduced H2O2 production, and improved high glucose-suppressed EPC functions by nitric oxide-related mechanisms. Conclusions: Our findings demonstrate that red wine consumption enhances blood flow recovery after tissue ischemia in diabetic mice. These effects may partly derive from enhanced EPC functions by upregulation of eNOS activity.

Original languageEnglish
Pages (from-to)426-435
Number of pages10
JournalAtherosclerosis
Volume212
Issue number2
DOIs
Publication statusPublished - Oct 2010

Fingerprint

Wine
Nitric Oxide
Ischemia
Ethanol
Glucose
Endothelial Progenitor Cells
NG-Nitroarginine Methyl Ester
Streptozocin
Bone Marrow Cells
Flow Cytometry
Up-Regulation
Extremities
Eating

Keywords

  • Diabetes
  • Endothelial progenitor cells
  • Nitric oxide
  • Red wine

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Moderate intake of red wine improves ischemia-induced neovascularization in diabetic mice-Roles of endothelial progenitor cells and nitric oxide. / Huang, Po Hsun; Tsai, Hsiao Ya; Wang, Chao Hung; Chen, Yung Hsiang; Chen, Jia Shiong; Lin, Feng Yen; Lin, Chih Pei; Wu, Tao Cheng; Sata, Masataka; Chen, Jaw Wen; Lin, Shing Jong.

In: Atherosclerosis, Vol. 212, No. 2, 10.2010, p. 426-435.

Research output: Contribution to journalArticle

Huang, Po Hsun ; Tsai, Hsiao Ya ; Wang, Chao Hung ; Chen, Yung Hsiang ; Chen, Jia Shiong ; Lin, Feng Yen ; Lin, Chih Pei ; Wu, Tao Cheng ; Sata, Masataka ; Chen, Jaw Wen ; Lin, Shing Jong. / Moderate intake of red wine improves ischemia-induced neovascularization in diabetic mice-Roles of endothelial progenitor cells and nitric oxide. In: Atherosclerosis. 2010 ; Vol. 212, No. 2. pp. 426-435.
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T1 - Moderate intake of red wine improves ischemia-induced neovascularization in diabetic mice-Roles of endothelial progenitor cells and nitric oxide

AU - Huang, Po Hsun

AU - Tsai, Hsiao Ya

AU - Wang, Chao Hung

AU - Chen, Yung Hsiang

AU - Chen, Jia Shiong

AU - Lin, Feng Yen

AU - Lin, Chih Pei

AU - Wu, Tao Cheng

AU - Sata, Masataka

AU - Chen, Jaw Wen

AU - Lin, Shing Jong

PY - 2010/10

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N2 - Objective: Circulating endothelial progenitor cells (EPCs) play a significant role in postnatal neovascularization. Patients with diabetes have attenuated EPC functions and impaired angiogenic response after tissue ischemia. We investigated whether moderate red wine consumption can enhance blood flow recovery in response to tissue ischemia by enhancement of EPC functions in diabetic mice. Methods and results: Starting at 4 weeks after diabetes onset, red wine (4ml/kg/day) or ethanol were administered to streptozotocin (STZ)-induced (type 1) diabetic mice and KKAy-Ta (type 2) mice. Unilateral hind limb ischemia surgery was conducted after 2 weeks of red wine or ethanol ingestion. Type 1 and type 2 diabetic mice given red wine, but not ethanol, had significantly increased collateral flow about 30% and augmented capillary density in ischemic tissues. These beneficial effects were markedly abolished by an eNOS inhibitor (L-NAME). Flow cytometry analysis showed impaired EPC-like cells (Sca-1+/Flk-1+) mobilization after ischemia surgery in diabetic mice, but augmented mobilization in red wine group (baseline vs. 2 days after operation: 0.88±0.06% vs. 1.73±0.29%, p=0.010). C-kit positive bone marrow cells isolated from diabetic mice given red wine had enhanced adhesion and migration compared to mice given vehicle. By in-vitro studies, incubation with red wine in high-glucose medium significantly reduced H2O2 production, and improved high glucose-suppressed EPC functions by nitric oxide-related mechanisms. Conclusions: Our findings demonstrate that red wine consumption enhances blood flow recovery after tissue ischemia in diabetic mice. These effects may partly derive from enhanced EPC functions by upregulation of eNOS activity.

AB - Objective: Circulating endothelial progenitor cells (EPCs) play a significant role in postnatal neovascularization. Patients with diabetes have attenuated EPC functions and impaired angiogenic response after tissue ischemia. We investigated whether moderate red wine consumption can enhance blood flow recovery in response to tissue ischemia by enhancement of EPC functions in diabetic mice. Methods and results: Starting at 4 weeks after diabetes onset, red wine (4ml/kg/day) or ethanol were administered to streptozotocin (STZ)-induced (type 1) diabetic mice and KKAy-Ta (type 2) mice. Unilateral hind limb ischemia surgery was conducted after 2 weeks of red wine or ethanol ingestion. Type 1 and type 2 diabetic mice given red wine, but not ethanol, had significantly increased collateral flow about 30% and augmented capillary density in ischemic tissues. These beneficial effects were markedly abolished by an eNOS inhibitor (L-NAME). Flow cytometry analysis showed impaired EPC-like cells (Sca-1+/Flk-1+) mobilization after ischemia surgery in diabetic mice, but augmented mobilization in red wine group (baseline vs. 2 days after operation: 0.88±0.06% vs. 1.73±0.29%, p=0.010). C-kit positive bone marrow cells isolated from diabetic mice given red wine had enhanced adhesion and migration compared to mice given vehicle. By in-vitro studies, incubation with red wine in high-glucose medium significantly reduced H2O2 production, and improved high glucose-suppressed EPC functions by nitric oxide-related mechanisms. Conclusions: Our findings demonstrate that red wine consumption enhances blood flow recovery after tissue ischemia in diabetic mice. These effects may partly derive from enhanced EPC functions by upregulation of eNOS activity.

KW - Diabetes

KW - Endothelial progenitor cells

KW - Nitric oxide

KW - Red wine

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