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Review
. 2021 Oct 25:12:766080.
doi: 10.3389/fphys.2021.766080. eCollection 2021.

The Role of Vascular Endothelial Growth Factor in Tendon Healing

Xueli Liu  1   2 , Bin Zhu  1 , Yujie Li  1 , Xinyue Liu  1 , Sheng Guo  3 , Chenglong Wang  3 , Sen Li  3 , Dingxuan Wang  1
Affiliations
Review

The Role of Vascular Endothelial Growth Factor in Tendon Healing

Xueli Liu et al. Front Physiol. .

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.

Keywords: VEGF; angiogenesis; neovascularization; tendon healing; vascular endothelial growth factor.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Release and mechanism of action of VEGF after tendon injury. VEGF, vascular endothelial growth factor; TGF-β, transforming growth factor-β; FGF, fibroblast growth factor; PDGF, platelet derived growth factor; IGF, insulin like growth factor.
FIGURE 2
FIGURE 2
The variation trend of gross VEGF concentration after tendon injury in various tendon injury models. VEGF, vascular endothelial growth factor.
FIGURE 3
FIGURE 3
The main factors for endogenous VEGF upregulation and two paradoxical roles for VEGF in tendons. HIF-1, hypoxia-inducible factor-1; IL-1β, interleukin-1β; IL-6, interleukin-6; IL-8, interleukin-8; VEGF, vascular endothelial growth factor; ECM, extracellular matrix; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinases.
See this image and copyright information in PMC

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