on January 5, 2006
Published online before print January 5, 2006, doi: 10.1161/01.ATV.0000202677.55012.a0
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Submitted on July 13, 2005
Accepted on December 21, 2005
Impact of Mouse Strain Differences in Innate Hindlimb Collateral Vasculature
Armin Helisch *;
From the Department of Experimental Cardiology (A.H., S.W., S.W., M.H., T.Z., U.B., W.S.), Max-Planck-Institute for Physiological & Clinical Research, Bad Nauheim, Germany; Angiogenesis Research Center & Section of Cardiology (A.H., M.D., U.B., J.D.P.), Dartmouth Medical School, Lebanon, NH; and EPR Center for Viable Biological Systems (N.K., H.M.S.), Dartmouth Medical School, Hanover, NH.
* To whom correspondence should be addressed. E-mail: Armin.Helisch{at}dartmouth.edu.
Objective--To assess the importance of genetic background for collateral artery development.
Methods and Results--C57BL/6, BALB/c and 129S2/Sv mice were studied after femoral artery ligation by laser Doppler imaging, visible light oximetry, TOF-magnetic resonance imaging, and treadmill testing; C57BL/6 and BALB/c also underwent electron paramagnetic resonance (EPR) oximetry, x-ray angiography, and histology. C57BL/6 had the least initial distal ischemia and most complete recovery. BALB/c had the most severe initial ischemia and poorest recovery. BALB/c had some vasodilatory reserve in their ligated limbs not seen in the other strains at 3 weeks. By in vivo TOF-magnetic resonance angiography, C57BL/6 had larger preexistent and developed collaterals. By x-ray angiography, C57BL/6 had a higher collateral-dependent filling score and number of visible collaterals immediately after femoral ligation and a higher number of visible collaterals at 1 week but not at 4 weeks. EPR oximetry and histology revealed hypoxia and tissue damage in regions of collateral growth of BALB/c but not C57BL/6 mice. In C57BL/6 BrdUrd uptake in the thigh was limited to larger vessels and isolated perivascular cells. Proliferative activity in collateral arterioles was similar in both strains.
Conclusions--Genetic differences in preexistent collateral vasculature can profoundly affect outcome and milieu for compensatory collateral artery growth after femoral artery occlusion.
Key words: angiogenesis • collateral circulation • hypoxia • mouse strains • vascular biology
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