Table.

Roles of major factors that regulate angiogenesis and capillary regression in CKD.

	Factor	Major mechanisms of action	Other biological effects
Proangiogenic factors	Angiopoietin-1	EC proliferation and migration	enhancement of inflammation proangiogenic effect (model- dependent)
	Fibroblast growth factor-2	activation of VEGF-VEGFR-2 signaling	enhancement of fibrogenesis
	Hepatocyte growth factor	EC proliferation and migration inhibition of leukocyte adhesion to ECs
	Hypoxia-inducible factor	upregulation of VEGF level	enhancement of fibrogenesis
	Nitric oxide	maintenance of quiescent phenotype of ECs
	PlGF	EC proliferation and migration	enhancement of inflammation
	Platelet-derived growth factor B	PC recruitment to vasculature	enhancement of fibrogenesis
	VEGF-A	EC proliferation and migration	proangiogenic effect (disease phase dependent) excessive amount causes vascular instability
Antiangiogenic factors	ADAMTS-1	inhibition of VEGF-VEGFR-2 signaling induction of vascular instability
	Angiopoietin-2	competitive inhibition of angiopoietin-1	proangiogenic effect under the presence of VEGF-A
	Angiostatin	induction of EC apoptosis	alleviation of inflammation
	Asymmetric dimethylarginine (ADMA)	inhibition of nitric oxide synthesis
	CD44	induction of EC apoptosis
	Endostatin	inhibition of VEGF-VEGFR-2 signaling
	Soluble fms-like tyrosine kinase-1 (sFlt-1)	trapping of circulating VEGF-A and PlGF
	Thrombospondin-1	inhibition of VEGF-VEGFR-2 signaling	enhancement of inflammation

Abbreviations: CKD, chronic kidney disease; ADAMTS-1, a disintegrin and metalloproteinase with thrombospondin motif-1; EC, endothelial cell; PC, pericyte; PlGF, placental growth factor; VEGF: vascular endothelial growth factor; VEGFR-2, VEGF receptor-2