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Age‐Dependent Impairment in Tissue Perfusion in the Foxn1nu/nu Nude Mouse: Potential for Better Predicting the Efficacy of Cell‐Based, Proangiogenic Therapies
Author(s) -
Brooks Benjamin David,
McKee Jeff
Publication year - 2009
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.23.1_supplement.1006.9
Subject(s) - hindlimb , angiogenesis , perfusion , therapeutic angiogenesis , medicine , ischemia , neovascularization , laser doppler velocimetry , limb perfusion , pathology , endocrinology , blood flow
The mouse model of hindlimb ischemia is used routinely to evaluate proangiogenic therapeutics. Most studies employ young mice (<12 wk) even though peripheral arterial disease is not a clinical issue in young patients. Young (12 wk), wild type mice are more efficient at angiogenesis versus old (2 yr) mice as shown by significantly higher hindlimb perfusion (measured by laser Doppler imaging, LDI) and capillary density, which were attributed to an age‐dependent impairment in endothelial function and VEGF expression (Rivard et al 1999). This suggests that old mice are more relevant for use in nonclinical development and may be more sensitive in detecting therapeutic effects as compared with young mice. The purpose of this work was to determine if a similar effect of age on angiogenesis was detectable in immunocompromised mice, specifically the Foxn1 nu/nu nude mouse, which is used routinely to evaluate cell‐based, proangiogenic therapeutics. Foxn1 nu/nu nude mice, 10 or 34 wk, underwent surgically induced, unilateral hindlimb ischemia. Hindlimb perfusion, measured by LDI was performed on days 1, 4, 7, 14 and 21 post‐surgery. Laser Doppler ratios (ischemic to nonischemic limb) were significantly lower in the old mice on days 4, 7, 14 and 21 compared to the young mice. These data indicate that older Foxn1 nu/nu nude mice recover hindlimb perfusion more slowly, presumably due to an age‐dependent impairment in angiogenesis. Baxter provided all research support.