The effect of hypoxia on plasma angiostatin and related factors in newborn pigs.
Hypoxia is a potent stimulus of angiogenic factors and angiostatin can inhibit angiogenesis. Little is known about the expression of angiostatin and its related factors in hypoxic newborns. Using a swine model of neonatal hypoxia, we hypothesized that hypoxia would decrease plasma levels of angiostatin in a time-dependent fashion. In this study newborn piglets underwent hypoxia (15-18% oxygen) for 3 hr, were allowed to recover in 21% oxygen and were then observed for 96 hr. Sham-operated piglets did not experience hypoxia. Plasma levels of angiostatin, plasminogen/plasmin, MMP-2 and -9, and VEGF were determined at normoxic baseline; at the end of hypoxia; at 5 hr; and at 96 hr post-hypoxia. Plasma levels of angiostatin, but not plasminogen/plasmin, decreased significantly at the end of hypoxia and 5 hr after hypoxia compared with the sham-operated group (P < 0.05). Plasma MMP-2 levels at the end of hypoxia were lower in the hypoxic group than in sham animals (P < 0.005). In the hypoxic but not sham-operated group, plasma levels of angiostatin and MMP-2 were positively correlated (r = 0.69; P < 0.001). Plasma MMP-9 and VEGF levels were not different between sham-operated and hypoxic groups and did not correlate with plasma angiostatin levels. In conclusion, hypoxia showed a transient suppressive effect on the expression of plasma angiostatin in newborn piglets. This may imply an inhibitory role of hypoxia on MMP-2 and the proteolytic cleavage of plasminogen to angiostatin.
Emara
Marwan
M
Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
Obaid
Laila
L
Johnson
Scott
S
Bigam
David L
DL
Cheung
Po-Yin
PY
D043168:Angiostatins / Q000097:blood*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D015153:Blotting, Western; D005341:Fibrinolysin / Q000378:metabolism; D000860:Hypoxia / Q000097:blood*; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D010958:Plasminogen / Q000378:metabolism; D013552:Swine; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D042461:Vascular Endothelial Growth Factor A; D043168:Angiostatins; D010958:Plasminogen; D005341:Fibrinolysin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9