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Homocysteine disrupts actin organization and vascular outgrowth by an iNOS‐dependent mechanism during angiogenesis
Author(s) -
Mayo Jamie Nadine,
Chen ChengHung,
Bearden Shawn E.
Publication year - 2013
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.27.1_supplement.685.5
Subject(s) - angiogenesis , motility , homocysteine , microbiology and biotechnology , mechanism (biology) , actin , hyperhomocysteinemia , chemistry , medicine , endocrinology , biology , andrology , philosophy , epistemology
Objective Hyperhomocysteinemia (HHcy) impairs angiogenesis. The goal of this study was to test the hypothesis that HHcy impairs angiogenic growth through an iNOS dependent mechanism. Methods We used an ex‐vivo adult mouse choroid tissue model of VEGF‐stimulated angiogenesis. Mouse microvascular endothelial cells were studied in culture in parallel experiments. Results 20μM homocysteine (Hcy) treatments significantly decreased the area of angiogenic outgrowth (8.9mm2 ± 0.31 vs 4.1mm2 ± 0.58; p<0.05). Hcy 1) canted the orientation of actin filaments (orientation in relation to explant center: 38.6ܰ±13.0ܰ vs 95.4ܰ± 6.5ܰ; p<0.05), 2) decreased the occurrence of cellular extensions beyond the leading edge of outgrowth (7 ± 0.89 vs 2.2 ±0.52; p<0.05), and 3) reduced the motility of dispersed cells (19.8μm/hr ±1.4 vs 13.1μm/hr ±1.7; p<0.05). Inhibition of iNOS with 1400W (10μM) rescued the effect of Hcy on area of outgrowth, occurrence of cellular extensions, and cell motility. Conclusions Hcy decreases angiogenic outgrowth by inhibiting motility and disrupting actin filament organization in part via an iNOS‐dependent mechanism. This work was supported by NIH grant #HL106548(SEB).