Improvement of neovascularization capacity of bone marrow mononuclear cells from diabetic mice by ex vivo pretreatment with resveratrol

Lu Gan, Hirohide Matsuura, Toshihiro Ichiki, Xinhua Yin, Ryohei Miyazaki, Toru Hashimoto, Juan Cui, Kotaro Takeda, Kenji Sunagawa

Research output: Contribution to journalArticle

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Abstract

Implantation of bone marrow-derived mononuclear cells (BMMCs) is known to accelerate blood flow recovery in a hindlimb ischemia model in mice. However, the neovascularization capacity of BMMCs from diabetic mice is impaired. Resveratrol, a natural polyphenolic compound abundant in red wine, is known to extend the lifespan of high cholesterol-fed mice. We tested whether resveratrol improves the neovascularization capacity of BMMCs from diabetic mice. Diabetes was induced by the injection of streptozotocin into C57B/6 mice. BMMCs from normal mice and diabetic mice were implanted into the ischemic limb induced by ligation of the unilateral femoral artery. Blood flow recovery measured by the laser Doppler method was significantly decreased in mice that received BMMCs from diabetic mice compared with BMMCs from normal mice. However, ex vivo treatment of BMMCs from diabetic mice, but not from normal mice, with resveratrol for 30min significantly improved blood flow recovery. Capillary density measured by PECAM-1 positive cells was significantly increased in mice that received either normal BMMCs or diabetic BMMCs treated with resveratrol. Treatment of BMMCs from diabetic mice with resveratrol increased mRNA expression of vascular endothelial growth factor and endothelial nitric oxide synthase and decreased production of reactive oxygen species. Resveratrol improved the impaired neovascularization capacity of BMMCs derived from diabetic mice. The effects of resveratrol may be due to a reduction of oxidative stress and an induction of angiogenic factors. Resveratrol may be beneficial by improving the neovascularization capacity of BMMCs in patients with diabetes mellitus.

Original languageEnglish
Pages (from-to)542-547
Number of pages6
JournalHypertension Research
Volume32
Issue number7
DOIs
Publication statusPublished - Jul 21 2009

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Bone Marrow Cells
Bone Marrow
resveratrol
CD31 Antigens
Nitric Oxide Synthase Type III
Angiogenesis Inducing Agents
Wine
Femoral Artery
Hindlimb
Streptozocin
Vascular Endothelial Growth Factor A
Ligation
Reactive Oxygen Species
Diabetes Mellitus
Oxidative Stress
Lasers
Ischemia
Extremities
Cholesterol

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Improvement of neovascularization capacity of bone marrow mononuclear cells from diabetic mice by ex vivo pretreatment with resveratrol. / Gan, Lu; Matsuura, Hirohide; Ichiki, Toshihiro; Yin, Xinhua; Miyazaki, Ryohei; Hashimoto, Toru; Cui, Juan; Takeda, Kotaro; Sunagawa, Kenji.

In: Hypertension Research, Vol. 32, No. 7, 21.07.2009, p. 542-547.

Research output: Contribution to journalArticle

Gan, Lu ; Matsuura, Hirohide ; Ichiki, Toshihiro ; Yin, Xinhua ; Miyazaki, Ryohei ; Hashimoto, Toru ; Cui, Juan ; Takeda, Kotaro ; Sunagawa, Kenji. / Improvement of neovascularization capacity of bone marrow mononuclear cells from diabetic mice by ex vivo pretreatment with resveratrol. In: Hypertension Research. 2009 ; Vol. 32, No. 7. pp. 542-547.
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