Chinese Journal of Tissue Engineering Research ›› 2010, Vol. 14 ›› Issue (20): 3650-3654.doi: 10.3969/j.issn.1673-8225.2010.20.010

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Feasibility of rosiglitazone to improve mobilization of endothelial progenitor cells and reduce vascular oxidative stress in vivo

Zhao Qing1, Wei Meng1, Zhao Bing-hui2   

  1. 1Department of Cardiology, 2Department of Radiology, Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai   200233, China
  • Online:2010-05-14 Published:2010-05-14
  • Contact: Wei Meng, Professor, Chief physician, Doctoral supervisor, Department of Cardiology, Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China weim.sjtu6h@hotmail.com
  • About author:Zhao Qing, Doctor, Associate chief physician, Department of Cardiology, Sixth People’s Hospital, Shanghai Jiao Tong University, Shanghai 200233, China zhaoqing2@medmail.com.cn
  • Supported by:

    the Program Foundation of Shanghai Science and Technology Committee, No. 05JC14031*

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Abstract:

BACKGROUND: The peroxisome proliferator-activated receptor γ (PPAR-γ) agonists are found to have the ability to mobilize the endothelial progenitor cells (EPCs) from bone marrow to the peripheral circulation. However, the exact mechanism of its mobilization is not determined. It was found that PPAR-γ agonists have the ability to reduce the oxidative stress in diabetic mice.

OBJECTIVE: To investigate whether PPAR-γ agonists, i.e., rosiglitazone, can mobilize endothelial progenitor cells via reducing oxidative stress in vivo.

MATERIALS: A total of 24 New Zealand white rabbits were randomly divided into normal group, control group, and rosiglitazone group, with 8 rabbits for each group. Control group and rosiglitazone group were fed with high cholesterol diet and underwent carotid injury; rosiglitazone group was intragastrically injected with rosiglitazone (1 mg/kg per day) at 1 day after operation, and the injection lasted for 4 weeks; normal group was fed saline and only underwent cut-off cervical skin. After 4 weeks of treatment, CD34+KDR+ cell number characterized as EPCs was measured by flow cytometry. Nitric oxide (NO) level and superoxide anion (O2.-) were evaluated by Greiss reaction and colorimetry. Endothelial cell nitric oxide synthase (eNOS) and NADPH oxidase subunit p22phox mRNA expression were determined by reverse transcription polymerase chain reaction (RT-PCR).

RESULTS AND CONCLUSION: A total of 24 rabbits were included in the final analysis. Compared with control group, number of EPCs, NO level, clearing ability of superoxide anion, and eNOS mRNA expression were significantly increased in the rosiglitazone group (P < 0.05), which were still lower than normal group (P < 0.05). NADPHp22phox mRNA expression in the rosiglitazone group was significantly lower than control group (P < 0.05) but closed to normal group (P > 0.05). There was no significant difference in blood glucose and blood fat. Rosiglitazone could mobilize EPCs in vivo independently by its metabolic effects. The underlying mechanism may be related with a reduction of NADPH oxidase and an increase of eNOS mRNA expression. It may contribute to reduced oxidative stress.

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