Comparative analysis of arterial compliance in mice genetically null for cathepsins K, L, or S

Victor O Omojola; Zaria Hardnett; Hannah Song; Hai Dong; David J Alexander; Adeola O Adebayo Michael; Rudolph L Gleason Jr; Manu O Platt

doi:10.1016/j.jbiomech.2022.111266

Comparative analysis of arterial compliance in mice genetically null for cathepsins K, L, or S

J Biomech. 2022 Oct:143:111266. doi: 10.1016/j.jbiomech.2022.111266. Epub 2022 Aug 27.

Authors

Victor O Omojola¹, Zaria Hardnett¹, Hannah Song¹, Hai Dong¹, David J Alexander¹, Adeola O Adebayo Michael¹, Rudolph L Gleason Jr², Manu O Platt³

Affiliations

¹ Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University, Atlanta, GA, USA.
² The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
³ Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory University, Atlanta, GA, USA. Electronic address: manu.platt@bme.gatech.edu.

PMID: 36088868
DOI: 10.1016/j.jbiomech.2022.111266

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.

Keywords: Arterial stiffening; Cathepsin; Collagenase; Elastase; Vascular remodeling.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Animals
Apolipoproteins E / genetics
Cardiovascular Diseases*
Carotid Arteries / physiology
Cathepsins / genetics
Cysteine
Elastin*
Mice
Mice, Inbred C57BL
Mice, Knockout
Pancreatic Elastase

Substances

Apolipoproteins E
Elastin
Cathepsins
Pancreatic Elastase
Cysteine

Abstract

Publication types

MeSH terms

Substances

Grants and funding