Negative pressure wound therapy improves the quantity and quality of wound angiogenesis in diabetic rats by regulating the Ang/Tie-2 system

Negative pressure wound therapy can accelerate wound healing by promoting angiogenesis. However, what and how the signal pathway regulated angiogenesis and vessels maturation, and how the microvesels changed at different stage after negative pressure wound therapy treatment during the wound healing remain unclear. This study aimed to investigate the underlying molecular mechanisms and signal pathways of negative pressure wound therapy on angiogenesis and vessel maturation. Deep partial-thickness wounds were created in diabetic rats, and relevant growth factors were determined. Negative pressure wound therapy increased the angiogenin-2 and α-smooth muscle protein expression levels, and decreased angiogenin-1/angiogenin-2 expression ratios and phosphorylation levels of tyrosine kinase receptor-2 at early stage (1st to 3rd day) of wound healing. At later stage (7th to 10th day) of wound healing, negative pressure wound therapy increased angiogenin-1, αsmooth muscle protein, angiogenin-1/angiogenin-2 ratios expression and phosphorylation levels of tyrosine kinase receptor-2, simultaneously increased microvessel pericyte coverage index. Negative pressure wound therapy may not only predominantly promote microvessels destabilization and thus increase the quantity of initial angiogenesis in the early stage but also preferentially promote microvessels stabilization and thus enhance the quality of formed vessels, contributing to vessels maturation. And a tyrosine kinase receptor-2 inhibitor could moderately influence angiogenesis process during the early stage but affect vascular remodeling and maturation process significantly during the later stage of wound healing. Furthermore, it demonstrated that angiogenin/tyrosine kinase receptor-2 signal pathway play a primary role in regulating the process of the vessel maturation.