Table 2.

Summary of the main genes and most genes encoding cell surface receptors on hypoxia-mediated angiogenesis modifications in the regulation of liver fibrosis

Angiogenic factors	Actions during angiogenesis	Role in angiogenesis in LF	Refs
VEGF	Promotes endothelial cell survival and homeostasis Promotes endothelial cell detachment from the basement membrane VEGF and Notch co-operate in an integrated intercellular feedback that functions as a “branching pattern generator”	Alterations in hepatic architecture may stimulate the development of liver fibrosis, increase the intrahepatic vascular resistance, and even develop into portal hypertension	[32, 33]
ANG1 and Tie-2	ANG1, produced by mural cells, activates its endothelial receptor Tie-2 ANG1 stabilizes vessels, promotes pericyte adhesion, and makes them leak resistant by tightening endothelial junctions	Autocrine ANG1 promotes HSC/myofibroblast migration	[29]
VEGFR1, R2	Sequesters VEGF and prevents its activation of VEGFR2	A negative endogenous modulator of angiogenesis	[30]
PDGF-BB	Recruitment of pericytes	Produced by ECs/LSECs this factor stimulates HSC proliferation, differentiation, and migration, as well as transforms HSC into myofibroblasts	[28]
ET-1	It is abundant in vascular smooth muscle cells, and its main task is to promote cell proliferation and mediate vascular contraction	Promotes the HSC contraction and the secretion of cell matrix by HSC	[27]