Antiangiogenic Therapy for Diabetic Nephropathy

Table 1

Candidates of endogenous antiangiogenic factors as therapeutic agents for diabetic nephropathy.

	Description	Target molecule	Effect on ECs	Clinical use
sFlt-1	Soluble form of VEGFR-1 that binds to circulating VEGF and prevents it from binding to VEGFR-2.	VEGF	Apoptosis	None
VEGF-A165b	Inhibitory VEGF-A splice variant which induces insufficient phosphorylation of VEGFR-2.	VEGFR-2		None
Tumstatin	Protein fragment cleaved from type IV collagen that binds to endothelium via integrin and inhibits protein synthesis.	αvβ3-integrin	Apoptosis	None
Endostatin	Protein fragment cleaved from type XVIII collagen which acts on endothelium to suppress cell cycle genes and antiapoptotic genes.	α5β1-integrin (glypicans,; VEGFR-2)	Apoptosis	Available; in China
Angiostatin	Protein fragment cleaved from plasminogen which binds to potentially many proteins to induce its apoptosis.	Angiomotin and	Apoptosis	Under trial
Vasohibin-1	Endothelium-derived protein that causes negative feedback response in endothelial cells stimulated by VEGF-A and promotes its survival by inducing SOD2 and Sirt1.	Unknown	Survival	None

ECs, endothelial cells; sFlt-1, soluble fms-like tyrosine kinase-1; VEGF, vascular endothelial growth factor; VEGFR-2, VEGF receptor-2; SOD2, superoxide dismutase-2; Sirt1, sirtuin-1. -A₁₆₅b may attenuate endothelial survival effect of VEGF-A₁₆₅, but endothelial protective effect was also reported (see text). representative molecules include surface ATP synthase, NG2 proteoglycan, c-Met, and annexin II.