Pressure-induced collagen degradation in arterial tissue as a potential mechanism for degenerative arterial disease progression

Abstract

Collagen fibre degradation is a strain-dependent process, whereby the magnitude of experienced strain dictates the rate of enzymatic cleavage. Studies have identified conflicting findings as to whether strain inhibits or enhances collagen degradation, which may be explained by the tissue type and tissue scale investigated, as well as the strain range considered. The aim of this study is to identify, for the first time, the strain-dependent degradation response of intact arterial vessels experiencing physiological pressures and apply these findings to a computational model to better understand degenerative arterial diseases, such as aneurysms.To achieve this, a series of quasi-static pressure inflation experiments were carried out on intact arteries in the presence of purified bacterial collagenase at physiologically relevant pressures to investigate collagen matrix degradation in the vascular wall. A complementary computational model was developed to explore the complex role of pressure, non-collagenous matrix contribution, and collagen fibre crimp in the ultimate degradation response of the vessel.Pressure induced inflation-degradation results identified an increased rate of vessel expansion and reduced time to failure with increasing pressure in the vessels. Interestingly, our computational model was able to capture this same response, including the elevated rates of degradation which occur at low pressures. These findings highlight the critical role of strain in collagen degradation, particularly in cases of arterial disease, such as aneurysm formation, whereby structural integrity may be compromised.