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- W3174433888 abstract "Reactive oxygen species (ROS) are implicated in coronary angiogenesis, collateral growth and cellular signaling. Here, we evaluated the requirement for superoxide (·O2−) and p38 MAPK activation in angiogenesis, in vitro, and coronary collateral development, in vivo. Both the flavin-containing oxidase inhibitor, DPI (10 μM) and the SOD inhibitor, DETC (10 mM) blocked VEGF-induced (100 ng/ml) endothelial cell (HCAEC) tube formation in Matrigel (p<0.05, n=10) even though they decreased and increased intracellular (·O2−), respectively (confirmed by DHE stain). Next, we assessed the effect of daily treatment with DPI (1 μM) and DETC (5 mM) on coronary collateral development in vivo, in a rat model of episodic ischemia: repetitive occlusion (RO) of LAD (40 sec, every 20 min, 3 times a day, for 10 days). In sham rats, native collateral flow (measured by microspheres) in the ischemic zone was 18±6% of the normal zone flow. In RO group, collateral flow in the ischemic zone was 83±5% of that in the normal zone. Blockade of ·O2− production by DPI prevented the increase in collateral flow (25±4% of normal zone, p<0.05, n=8). Increasing ·O2− by SOD inhibition achieved similar results (collateral flow was 21±2% of normal zone, p<0.05, n=8). Both DPI and DETC blocked RO-induced p38 MAPK activation in response to VEGF in vitro and to RO in vivo. p38 MAPK inhibition prevented HCAEC tube formation and partially blocked (42±7% of normal zone flow, n=8) RO-induced coronary collateral development. These results demonstrate a requirement for optimal superoxide concentration and p38 MAPK activation in angiogenesis and coronary collateral development." @default.
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- W3174433888 date "2006-03-01" @default.
- W3174433888 modified "2023-09-27" @default.
- W3174433888 title "Optimal ROS concentration and p38 MAP kinase are required for coronary collateral development" @default.
- W3174433888 doi "https://doi.org/10.1096/fasebj.20.4.a718-b" @default.
- W3174433888 hasPublicationYear "2006" @default.
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