Premium
ICAM‐1 Governs Angiogenesis via Redox Regulation of PTEN Expression and eNOS activity
Author(s) -
Langston John William,
Chidlow John H.,
Teng Xinjun,
Patel Rakesh P.,
Kevil Christopher G.
Publication year - 2006
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.20.4.a720-a
Subject(s) - pten , enos , angiogenesis , redox , chemistry , cancer research , microbiology and biotechnology , biochemistry , biology , pi3k/akt/mtor pathway , apoptosis , nitric oxide synthase , enzyme , organic chemistry
eNOS derived NO is critical in the angiogenic process, thus understanding the mechanisms regulating eNOS activity during angiogenesis are crucial. Here we present data showing that ICAM‐1 is a novel effector of VEGF 164 induced eNOS function, endothelial cell chemotaxis, and angiogenesis. VEGF 164 mediated angiogenesis in WT and ICAM‐1 −/− mice was assessed in vivo using a Millipore disk assay. VEGF 164 chemotaxis of mouse aortic endothelial cells (MAEC) was measured by transwell assay. eNOS activity was assessed using western blot analysis of phosphorylation at ser 1177 and DAF‐FM fluorescence. PTEN expression was assessed by western blot. VEGF 164 mediated angiogenesis in vivo was significantly decreased in ICAM‐1 −/− mice compared to WT mice. ICAM‐1 −/− MAEC showed impaired VEGF 164 mediated chemotaxis, eNOS phosphorylation, and NO production vs. WT MAEC. PTEN expression was significantly elevated in ICAM‐1 −/− MAEC which was controlled by intracellular glutathione levels, as 150 μM BSO treatment returned PTEN expression to WT levels and restored VEGF 164 chemotaxis and eNOS phosphorylation. Likewise, 5 mM glutathione ethyl ester (GEE) supplementation of WT cells recapitulated ICAM‐1 −/− chemotactic defects, increased PTEN expression, and blocked eNOS phosphorylation. These data suggest a novel role for ICAM‐1 in modulating VEGF 164 induced angiogenesis and eNOS activity via regulation of intracellular glutathione levels which regulate PTEN expression.