Cathepsin K, L, and S Differentially Regulate Arterial Compliance in Mouse Carotid Arteries

Cysteine cathepsins are potent lysosomal proteases implicated in cardiovascular diseases such as atherosclerosis, sickle cell disease, and aneurysms. Proteolytic action by cathepsins degrades various substrates in the vasculature, most notably ECM, whose structure and integrity determine the mechanical behavior of arteries. Small animal models utilizing cathepsin knockout and atherogenic diets have been used to study changes in biomechanics in cardiovascular disease, but knowledge of the impacts of cathepsin knockout on non-atherosclerotic arterial mechanics are scarce. We aim to examine arterial mechanics in several cathepsin knockout lines (CatK^-/-, CatL^-/- and CatS-/-) 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. Pressure-diameter data revealed CatL^-/- arteries were smaller in caliber compared to CatK^-/-, CatS^-/-, and ApoE^-/- controls and were less compliant than ApoE^-/- and CatS^-/- arteries at lower pressures, where elastin governs the mechanical response. CatK^-/- arteries had showed increased in vivo strains compared to CatL^-/- and CatS^-/- arteries. CatL^-/- arteries were less compliant than ApoE^-/- and CatS^-/- arteries pressurized to sub-diastolic pressures,. Taken together, the data suggests that the loss of the potent collagenase cathepsin K increases axial and circumferential arterial compliance, while knockout of the elastase cathepsin L decreased circumferential arterial compliance, and knockout of the elastase cathepsin S showed no impact on arterial mechanics.