Advances in neovascularization after diabetic ischemia

Table 2 Mechanisms and functions of the antiangiogenic factors

Inhibitory factor	Mechanism	Function	Ref.
Platelet reactive protein-1 (TSP-1)	TSP-1 levels increase under hypoxia	TSP-1 inhibits angiogenesis by stimulating endothelial cell apoptosis and inhibiting endothelial cell migration and proliferation as well as inhibiting VEGF and eNOS	[42,43]
IL-12	IL-12 stimulates the expression of proinflammatory and antiangiogenic genes in monocytes	Neutralization of IL-12 can enhance angiogenesis in ischemic areas and reduce body dysfunction	[7,44]
Noncoding RNAs	Noncoding RNA has the dual role of promoting and inhibiting angiogenesis	Upregulation of MiR-15a and MiR-16 reduce Tie2 protein levels and inhibit angiogenesis	[35,36]

eNOS: Endothelial nitric oxide synthase; IL-12: Interleukin 12; MiR: MicroRNA; TSP-1: Thrombospondin-1; VEGF: Vascular endothelial growth factor.