Premium
A role for βENaC protein in microvessel formation
Author(s) -
Adair Thomas H.,
Drummond Heather A.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.1031.5
Subject(s) - epithelial sodium channel , angiogenesis , microvessel , western blot , chemistry , medicine , endocrinology , blot , biology , biochemistry , sodium , gene , organic chemistry
Previous studies demonstrate that β Epithelial Na+ Channel (βENaC) is required for vascular smooth muscle cell migration, an essential step in angiogenesis. However, the importance of βENaC in angiogenesis is unknown. We tested the hypothesis that VEGF can stimulate angiogenesis by upregulating βENaC expression using the rat aortic ring angiogenesis model. Cultures were treated with VEGF (50 ng/ml) and the ENaC inhibitor benzamil (0.1, 1 and 10 μM) over 6–8 days. The lowest dose of benzamil inhibited 44% of new microvessels formed in VEGF treated cultures, whereas 1 and 10 μM benzamil abolished VEGF induced growth. To determine if VEGF stimulates expression of βENaC protein, we evaluated the effect of VEGF on βENaC expression using Western blotting in a pooled sample of aortic rings and semi‐quantitative immunolabeling of newly formed microvessels. We found that VEGF increased βENaC expression in proportion to vessel outgrowth (~2 fold). To determine if VEGF mediated angiogenesis requires βENaC protein, we evaluated aortic ring microvessel formation in a mouse model of reduced βENaC. We found that microvessel formation was inhibited >50% at day 8. The results indicate that 1) VEGF stimulates βENaC expression and 2) VEGF mediated angiogenesis in the aortic ring model requires normal βENaC expression. (HL‐51971, HL‐086996).