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Tumor necrosis factor inhibition increases the revascularization of ischemic hind-limbs in diabetic mice

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Abstract

Tumor necrosis factor (TNF) is first identified as a mediator of lethal endotoxin poisoning. The anti-TNF therapy in the treatment of rheumatoid arthritis is based on the recognition of the role of TNF as the master regulator. Type II diabetes is characterized with altered stem cells and reduced vasculogenesis. Therefore, we aimed to determine if TNF inhibitor would improve vasculogenesis in ischemic hind-limbs of diabetic mice. Fifty male type 2 diabetic and their control (8–10 weeks old mice) were used, and ischemia was induced in the hind-limbs of all mice for 28 days. Vessel density was assessed by high-definition microangiography at the end of the treatment period. After 4 weeks, vessel density displayed no difference between the ischemic and the non-ischemic legs in control mice. However, in diabetic mice, the ischemic hind-limb vessel density was significantly decreased. Interestingly, diabetic mice displayed a significant improved vasculogenesis when treated with TNF inhibitor. Moreover, this data was confirmed by capillary density determined by immunostaining. TNF inhibitors are able to improve the formation of microvessels in response to ischemia in type 2 diabetes.

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Acknowledgments

The authors appreciate the helpful scientific revision from Prof. Dr. M.F. Ramadan (Institute of Scientific Research and Revival of Islamic Heritage, Umm Al-Qura University, Makkah, KSA)

Sources of funding

The authors would like to thank the Institute of Scientific Research and Revival of Islamic Heritage at Umm Al-Qura University (Project ID 43309046) for the financial support.

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None.

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Authors and Affiliations

  1. The Institute of Scientific Research and Revival of Islamic Heritage, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia

    Adel M. A. Assiri & Ali H. Amin

  2. Biochemistry Department, Faculty of Medicine, Umm Al-Qura University, Makkah, Kingdom of Saudi Arabia

    Adel M. A. Assiri

  3. Biochemistry Department, Genetic Engineering and Biotechnology Division, National Research Centre, Cairo, Egypt

    Hatim A. El-Baz

  4. Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt

    Ali H. Amin

Authors
  1. Adel M. A. Assiri
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  2. Hatim A. El-Baz
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  3. Ali H. Amin
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Correspondence to Ali H. Amin.

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Assiri, A.M.A., El-Baz, H.A. & Amin, A.H. Tumor necrosis factor inhibition increases the revascularization of ischemic hind-limbs in diabetic mice. Naunyn-Schmiedeberg's Arch Pharmacol 388, 1053–1060 (2015). https://doi.org/10.1007/s00210-015-1138-x

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  • DOI: https://doi.org/10.1007/s00210-015-1138-x

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