Source
Department of Biomedical Imaging, Genentech, Inc., South San Franscisco, California 94080, USA. jgreve@gene.com
Abstract
PURPOSE:
To develop magnetic resonace imaging (MRI) methods for functional assessment of arteriogenesis in a murine model of peripheral artery disease to quantify the influences of vascular endothelial growth factor (VEGF), age, and atherosclerosis.
MATERIALS AND METHODS:
Reactive hyperemia (RH), which was induced using a device designed for remote and transient occlusion of the aorta and vena cava, was measured by blood-oxygen-level-dependent MRI. Twenty-eight days after femoral artery ligation, peak height (PH) and time to peak (TTP) of the RH response was compared with sham-operated animals in 10-week-old C57Bl6, 9-month-old C57Bl6, and 9-month-old Ldlr(-/-)Apobec(-/-) mice. The contribution of VEGF to functional recovery was assessed in young mice. Angiogenesis was quantified using an anti-PECAM1 radioimmunoassay.
RESULTS:
In young animals, angiogenesis was maximal 7 days after ligation, whereas functional recovery took 28 days. Inhibition of VEGF eliminated the angiogenesis seen at 7 days and reduced RH (PH, P < 0.05). At day 28, RH was altered in old (TTP, P < 0.05) and atherosclerotic (PH, P < 0.05; TTP, P < 0.05) animals. RH was different in young, old, and atherosclerotic sham animals. Old and atherosclerotic mice showed reduced angiogenesis.
CONCLUSION:
The method presented herein can provide a sensitive assay for the functional assessment of arteriogenesis and highlights the contribution of VEGF, age, and atherosclerosis to this process.
(c) 2008 Wiley-Liss, Inc.