The Role of Vascular Endothelial Growth Factor in Tendon Healing.

Xueli Liu,Xinyue Liu,Chenglong Wang,Sheng Guo,Sen Li,Bin Zhu,Dingxuan Wang,Yujie Li

doi:10.3389/fphys.2021.766080

Abstract

Angiogenesis is crucial to facilitate tendon healing, such as delivering oxygen and nutrients, removing waste products, and controlling immune responses. Vascular endothelial growth factor (VEGF) is one of the most vital angiogenic factors that regulate blood vessel formation in tendon healing. Recently, biological therapies, including the application of exogenous VEGF, have been attracting increasing attention. However, at present, the effect of the application of exogenous VEGF in tendon healing is controversial, as the role of endogenous VEGF in tendons has also not been fully elucidated. This article will summarize the role of both endogenous and exogenous VEGF in tendon healing and discuss possible reasons for the controversy. The present review shows that tendon repair is facilitated only by proper angiogenesis and VEGF at the early stage, whereas the persistent high VEGF expression and prolonged presence of blood vessels may impair tendon repair at a later stage.

Highlights

Tendon is a specialized connective tissue that efficiently transfers muscle strength to the bone
We cannot deny the importance of early neovascularization for nutrition at the injury site, and we can identify Vascular endothelial growth factor (VEGF)-mediated extracellular matrix (ECM) degradation as a negative side-effect accompanied by neovascularization during the remodeling phase (Petersen et al, 2003b)
Tendon repair is facilitated only by proper angiogenesis and VEGF at an early stage, whereas the prolonged presence of blood vessels and persistent high VEGF expression may impair tendon repair at a later stage

Summary

INTRODUCTION

Tendon is a specialized connective tissue that efficiently transfers muscle strength to the bone. Because of the importance of neurovascular crosstalk in tissue repair (vascular arterial branching is precisely controlled by the pattern of peripheral nerves branching), increased NGF after acute injury promotes innervation, which in turn may upregulate nerve-derived VEGF (Li et al, 2013, 2019; Lee et al, 2021) This expression of VEGF could reflect a tentative tendon healing process (Kaux et al, 2014). The positive effects of plasmid DNA encoding VEGF164 and FGF2 genes were reported in two case reports (Kovac et al, 2017; Aimaletdinov et al, 2020) These studies support the positive effect of exogenous VEGF by promoting angiogenesis on tendon repair, such as enhancing type I collagen synthesis and increasing the mechanical properties of tendons in the early stage of tendon healing. Some studies indicated that anti-angiogenic treatment in tendon models may lead to improved tendon collagen organization and TABLE 1 | Summary of results and characteristics of the studies which investigated the effects of exogenous VEGF (or VEGF inhibitor) in tendon healing

Conclusion

DISCUSSION

CONCLUSION