Expression of angiogenesis factors in human umbilical vein endothelial cells and their regulation by PEDF.
The VEGFs and FGF-2 stimulate angiogenesis. Pigment epithelium-derived factor (PEDF) and thrombospondin-1 (TSP-1) strongly inhibit angiogenesis. Human umbilical vein endothelial cells (HUVECs) expressed VEGF-A, -B, -C, the VEGF receptors R1, R2, and R3, PEDF, FGF-2, and TSP-1, but VEGF-D transcripts were barely detectable. Hypoxia reduced the transcript levels of VEGF-C and its cognate receptor, VEGF-R3. PEDF blocked the effect of CoCl(2) on these two factors. The expression of VEGF-A and -B as well as VEGF-R1 and VEGF-R2 remained unchanged after exposure to hypoxia, PEDF, or both. There was a marked reduction in TSP-1 transcripts in CoCl(2) treated cultures and PEDF blocked this reduction. PEDF induced a small increase in FGF-2 transcripts in HUVECs, but there was no change in FGF-2 expression in HUVECs exposed to hypoxia or hypoxia plus PEDF. PEDF may control neovascularization, in part, by restoring the negative effects of hypoxia on the expression of a potent angiogenesis inhibitor, TSP-1. PEDF may also modulate vascular leakage by maintaining the transcriptional levels of the vascular homeostasis factors, VEGF-C and VEGF-R3 in hypoxic conditions.
Aparicio
S
S
Pharmaceutical Sciences, University of Missouri Kansas City, USA.
Sawant
S
S
Lara
N
N
Barnstable
C J
CJ
Tombran-Tink
J
J
D043924:Angiogenesis Modulating Agents / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005136:Eye Proteins / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D000860:Hypoxia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000494:pharmacology*; D019700:Thrombospondin 1 / Q000235:genetics; D014471:Umbilical Veins / Q000166:cytology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D000099174:Pigment Epithelium-Derived Factor
D043924:Angiogenesis Modulating Agents; D005136:Eye Proteins; D016222:Fibroblast Growth Factor 2; D009414:Nerve Growth Factors; D010100:Oxygen; D040262:Receptors, Vascular Endothelial Growth Factor; D015843:Serpins; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor