Impact of Mouse Strain Differences in Innate Hindlimb Collateral Vasculature

Abstract

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, time-of-flight-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 Ⅲ collateral circulation Ⅲ hypoxia Ⅲ mouse strains Ⅲ vascular biology P re-existent interarterial anastomoses have been identified in the coronary, cerebral, and peripheral circulation of various species. 1 The number and size of these anastomoses varies between species and tissues, resulting in different degrees of protection after arterial occlusion. 1 Pre-existing collateral arterial connections have been found in human hearts without evidence for coronary artery disease. 1-3 Remodeling of preexistent arterioles into mature collateral arteries has been observed in dog hearts, 4 hindlimbs of rabbits, 5-7 rats, 8 and mice, 9 and this process has been suggested to be the dominant mechanism responsible for the restoration of blood flow after arterial occlusion. 10 -12 Previously, we identified differences in perfusion recovery by laser Doppler imaging (LDI) after femoral artery occlusion in inbred strains of mice and attributed these to marginal differences in growth rates of collateral arterioles. 9 However, this study was limited by the fact that LDI and visible light oxygen spectrometry were the only comparative methods of in vivo assessment and histology was confined to isolated gracilis muscle collaterals with minimal surrounding tissue. Diameters of preexistent collaterals on the gracilis muscle were not significantly different between strains.In this study we examined collateral artery development and related parameters after femoral artery ligation in C57BL/6, 129S2 and BALB/c mice using the most comprehensive approach ever attempt...

Dynamic changes in murine vessel geometry assessed by high‐resolution magnetic resonance angiography: A 9.4T study

“…Furthermore, the time course of collateral vessel formation after ligation (Fig. 9) shows that blood flow is continuously increasing from day 3 to day 21, which is in good agreement with data obtained from laser Doppler imaging (9).…”

Activation of the Lectin Pathway by Natural IgM in a Model of Ischemia/Reperfusion Injury

“…To address this question, mice genetically deficient in C1q were characterized in the mesenteric I/R model. Because C1q Ϫ/Ϫ mice were in the C57BL/6 genetic background and MBL Ϫ/Ϫ mice were in the 129/B6 genetic background, WT mice with a C57BL/6 genetic background were used as controls for C1q Ϫ/Ϫ mice to prevent a biased conclusion influenced by genetic background (63)(64)(65)(66). In contrast to MBL Ϫ/Ϫ mice, the injury levels in C1q Ϫ/Ϫ mice were similar to those of WT animals (pathology scores: 25 Ϯ 21% vs 22 Ϯ 17%, respectively; Fig.…”

Multi-scale Computational Models of Pro-angiogenic Treatments in Peripheral Arterial Disease

“…51 In addition, average capillary blood velocity is higher in rats that have undergone exercise training. 3 Thus, using empirical relationships for viscosity and hematocrit distribution, 25,46 and experimental measurements of blood oxygenation and velocity in ligated rat EDL 3,16,17,44,46 we simulated blood flow for perfused tissue and partially perfused tissue (where only half of the tissue arterioles have blood flow).…”

“…The blood oxygen saturation in the inlet arterioles (SO 2A ) plummets following ligation, and slowly recovers to the healthy value of 0.6-0.8 over 2 weeks. 23,64 Based on measurements of tissue PO 2 and hemoglobin saturation calculations 16,17,44 we estimate SO 2A to be 0.06, 0.3, and 0.6 at 2, 7, and 14 days following ligation, respectively.…”

“…8,18 At rest, the recovery in tissue oxygen content is sufficient, but limb activity is hindered as exercise exerts demands on the provision of oxygen to the tissue. 3,17,44 Our models of VEGF transport in EDL muscle have been applied to resting muscle, 31 exercising muscle, 32 and a femoral ligation model of PAD in resting and exercising muscle. 24 Here, we apply the model to the prediction of VEGF concentration and VEGF gradient formation following three post-ligation therapeutic interventions in EDL muscle: VEGF gene therapy, using an adenoassociated virus (AAV)-type construct; VEGF cellbased therapy, using VEGF-overexpressing myoblasts that incorporate into muscle tissue following injection; and chronic exercise, which increases VEGF receptor expression, and therefore increases the signaling potential of VEGF.…”