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Conditional deletion of FoxO1/3/4 improves recovery from hindlimb ischemia
Author(s) -
Haas Tara,
Roudier Emilie,
Birot Olivier,
Doyle Jennifer,
Czyszek Justyna,
Milkiewicz Malgorzata
Publication year - 2011
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.25.1_supplement.1092.2
Subject(s) - hindlimb , ligation , foxo1 , hindiii , endocrinology , medicine , arteriogenesis , chemistry , ischemia , western blot , microbiology and biotechnology , biology , andrology , gene , biochemistry , transcription factor , restriction enzyme
FoxO proteins have anti‐proliferative and angiostatic functions. We recently reported increased FoxO1 protein in rat skeletal muscle capillaries following hindlimb ischemia induced by iliac artery ligation. We hypothesized that reduction of FoxO protein would improve capillary growth post‐ligation. We utilized a mouse model of conditional deletion of FoxO1/3/4 genes. MxCre − :FoxO1/3/4 f/f (Cre−) or MxCre + :FoxO1/3/4 f/f (Cre+) mice were injected with poly inosine:cytosine (pIC) to activate Cre expression, or phosphate‐buffered saline (PBS), 1 week prior to femoral artery ligation or sham surgery (n=4–6/group). After 10 days, Laser Doppler flow measurements were recorded and hindlimb muscles were removed to analyze capillary to fiber ratio (C:F). FoxO deletion, assessed by PCR analysis of genomic DNA, was observed in Cre+, but not Cre‐, mice injected with pIC. At day 10 post‐ligation, blood flow ratio (ischemic:contralateral leg) was 0.5 +/−0.09 and 0.8 +/−0.09 in Cre− and Cre+ mice, respectively (p<0.05). 10 days post‐ligation, C:F was 0.91+/−0.08 and 1.32+/−0.03 in Cre‐ and Cre+ mice respectively (p<0.05), compared with 1.04+/−0.04 and 1.16+/−0.08 in respective sham mice. These data support a signifcant role for FoxO proteins in regulating capillary growth and blood flow recovery to the ischemic mouse hindlimb. Funded by CIHR.