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Regulation of exercise induced endothelial sprout formation by FoxO1/3/4
Author(s) -
Liu Sammy T.K.,
Slopack Dara,
Roudier Emilie,
Haas Tara L.
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.685.15
Subject(s) - foxo1 , angiogenesis , medicine , endocrinology , chemistry , microbiology and biotechnology , biology , phosphorylation , protein kinase b
Forkhead Box “O” (FoxO) transcription factors have been shown to negatively regulated the process of capillary growth, but their influence on endothelial sprout initiation is not known. Mice with endothelial cell (EC) directed deletion of FoxO1/3/4 (FoxOΔ) have accelerated angiogenesis in response to repeated bouts of endurance exercise. We hypothesize this occurs due to FoxO regulation of genes such as Delta‐like1 (Dll1) and Tyrosine‐protein kinase receptor (Tek), which are involved in sprout formation and capillary maturation. EC with a deletion of FoxO1/3/4 showed decreases in Dll1 and Tek mRNA by 0.35 and 0.50 fold, respectively. Dll1 expression was significantly down‐regulated in mouse gastrocnemius muscle after 7 and 14 days of treadmill running, coinciding with the period of FoxO down‐regulation and capillary sprouting. In contrast, Tek expression was bi‐phasic, increasing two‐fold in animals trained for 1 and 14 days compared to sedentary counterparts. In FoxOΔ mice, basal Dll1 mRNA was reduced compared to wildtype, and there was no further decrease with training. The up‐regulation of Tek seen after 14 days of exercise was abolished in FoxOΔ animals. Our results indicate that Dll1 and Tek are novel FoxO targets, and their regulation with repeated exercise bouts may assist in the process of sprout formation and subsequent capillary maturation.