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Methods for Acute and Subacute Murine Hindlimb Ischemia

Methods for Acute and Subacute Murine Hindlimb Ischemia

Published on: June 21, 2016

Strain-dependent variation in collateral circulatory function in mouse hindlimb.

Dan Chalothorn¹, James E Faber

¹Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599-7545, USA.

Physiological Genomics

|June 17, 2010

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Genetic background significantly impacts collateral circulation and recovery from ischemia. Differences in native collaterals and their remodeling capacity, influenced by genes on chromosome 7, affect outcomes in obstructive arterial disease.

Area of Science:

Cardiovascular Biology
Genetics
Vascular Biology

Background:

Collateral circulation's extent and remodeling capacity are crucial for mitigating ischemic injury in obstructive arterial disease.
Genetic and environmental factors are suspected to influence these vascular parameters, but specific mechanisms remain unclear.

Purpose of the Study:

To investigate if genetic differences in collateral extent and remodeling underlie observed variations in perfusion recovery after femoral artery ligation among mouse strains.
To identify genetic loci and specific alleles contributing to differences in collateral function and ischemic outcomes.

Main Methods:

Comparative analysis of collateral density and remodeling in BALB/c, A/J, and C57BL/6 mouse strains following femoral artery ligation.
Utilized chromosome substitution strains (A/J --> C57BL/6) and F1 hybrids (C57BL/6 x BALB/c) to map genetic contributions.

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Laser Doppler Perfusion Imaging in the Mouse Hindlimb

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Published on: April 18, 2021

Assessed perfusion recovery, hindlimb use impairment, and ischemia severity.

Main Results:

BALB/c and A/J mice exhibited fewer native collaterals, reduced perfusion, slower recovery, and greater impairment compared to C57BL/6 mice.
A/J mice showed more robust collateral remodeling than BALB/c mice.
Alleles on chromosome 7 were confirmed to influence collateral function, with C57BL/6 alleles showing dominance.

Conclusions:

Genetic background profoundly influences collateral circulation and the response to ischemic events.
Variations in collateral extent and remodeling, particularly those linked to chromosome 7, are key determinants of ischemic injury severity.
The study highlights the importance of genetic factors in understanding and potentially treating obstructive arterial disease.