The Contribution of Glycosaminoglycans/Proteoglycans to Aortic Mechanics in Health and Disease: A Critical Review

While elastin and collagen have received a lot of attention as major contributors to aortic biomechanics, glycosaminoglycans (GAGs) and proteoglycans (PGs) recently emerged as additional key players whose roles must be better elucidated if one hopes to predict aortic ruptures caused by aneurysms and dissections more reliably. GAGs are highly negatively charged polysaccharide molecules that exist in the extracellular matrix (ECM) of the arterial wall. In this critical review, we summarize the current understanding of the contributions of GAGs/PGs to the biomechanics of the normal aortic wall, as well as in the case of aortic diseases such as aneurysms and dissections. Specifically, we describe the fundamental swelling behavior of GAGs/PGs and discuss their contributions to residual stresses and aortic stiffness, thereby highlighting the importance of taking these polyanionic molecules into account in mathematical and numerical models of the aorta. We suggest specific lines of investigation to further the acquisition of experimental data to complement simulations and solidify our current understanding. We underscore different potential roles of GAGs/PGs in thoracic aortic aneurysm (TAAD) and abdominal aortic aneurysm (AAA). Namely, we report findings according to which the accumulation of GAGs/PGs in TAAD causes stress concentrations which may be sufficient to initiate and propagate delamination. On the other hand, there seems to be no clear indication of a relationship between the marked reduction in GAG/PG content and the stiffening and weakening of the aortic wall in AAA.