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Updated: Aug 29, 2025
Assessing Murine Resistance Artery Function Using Pressure Myography
Published on: June 7, 2013
Comparative analysis of arterial compliance in mice genetically null for cathepsins K, L, or S
Victor O Omojola1, Zaria Hardnett1, Hannah Song1
1Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
Abstract:
Cysteine cathepsins are potent proteases implicated in cardiovascular disease for degrading extracellular matrix (ECM) whose structure and integrity determine the mechanical behavior of arteries. Cathepsin knockout mouse models fed atherogenic diets have been used to study their roles in cardiovascular disease, but the impacts of cathepsin knockout on non-atherosclerotic arterial mechanics are scarce. We examine arterial mechanics in several cathepsin knockout mouse lines (CatK-/-, CatL-/-ApoE-/- and CatS-/-ApoE-/-) and controls (C57/Bl6, apolipoprotein E-/-). Common carotid arteries of three month-old mice were isolated and underwent biaxial mechanical testing and opening angle tests. Measured wall thicknesses and pressure-diameter curves were fed into a 4-fiber constitutive model to assess differences in material properties. Pressure-diameter data revealed CatL-/-ApoE-/- arteries were smaller in caliber compared to CatK-/-, CatS-/-ApoE-/- and ApoE-/- controls and were less compliant than ApoE-/- and CatS-/-ApoE-/- arteries at lower pressures, where elastin governs the mechanical response. CatK-/- arteries showed increased in vivo axial stretches compared to CatL-/-ApoE-/- and CatS-/-ApoE-/- arteries. CatL-/-ApoE-/- arteries were less compliant than ApoE-/- and CatS-/-ApoE-/- arteries pressurized to sub-diastolic pressures. 4-fiber and unified fiber distribution models were able to capture arteries' nonlinear mechanical responses; calculated material parameters suggested that ApoE-/- arteries had increased axial parameters compared to CatL-/-ApoE-/- and CatS-/-ApoE-/- arteries. Taken together, the data suggests that loss of the potent collagenase catK increases axial and circumferential arterial compliance, while knockout of the elastase catL decreased circumferential arterial compliance, and knockout of the elastase catS showed no impact on carotid arterial mechanics.
Insights
Loss of cathepsin K (CatK) increased arterial compliance, while loss of cathepsin L (CatL) decreased it. Cathepsin S (CatS) knockout had no effect on carotid artery mechanics in mice.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Protease Function
Background:
- Cysteine cathepsins degrade extracellular matrix (ECM), impacting arterial mechanical properties.
- Previous studies focused on cathepsin roles in atherosclerosis; non-atherosclerotic mechanics are less understood.
Purpose of the Study:
- To investigate the impact of cathepsin knockout on non-atherosclerotic arterial mechanics.
- To elucidate the specific roles of CatK, CatL, and CatS in determining carotid artery mechanical behavior.
Main Methods:
- Biaxial mechanical testing and opening angle tests on common carotid arteries from cathepsin knockout and control mice.
- Analysis using a 4-fiber constitutive model to determine material properties.
- Comparison of arterial caliber, compliance, and mechanical parameters.
Main Results:
- Cathepsin L (CatL) knockout arteries were smaller and less compliant at low pressures compared to controls.
- Cathepsin K (CatK) knockout arteries exhibited increased in vivo axial stretches.
- Loss of CatK increased arterial compliance, while loss of CatL decreased it; CatS had no significant effect.
Conclusions:
- CatK, a collagenase, influences arterial axial and circumferential compliance.
- CatL, an elastase, negatively impacts circumferential arterial compliance.
- Cathepsin knockout significantly alters arterial mechanics, highlighting their distinct roles beyond atherosclerosis.
