Most computational models of abdominal aortic aneurysms address either the hemodynamics within the lesion or the mechanics of the wall. More recently, however, some models have appropriately begun to account for the evolving mechanics of the wall in response to the changing hemodynamic loads. Collectively, this large body of work has provided tremendous insight into this life-threatening condition and has provided important guidance for current research. Nevertheless, there has yet to be a comprehensive model that addresses the mechanobiology, biochemistry, and biomechanics of thrombus-laden abdominal aortic aneurysms. That is, there is a pressing need to include effects of the hemodynamics on both the development of the nearly ubiquitous intraluminal thrombus and the evolving mechanics of the wall, which depends in part on biochemical effects of the adjacent thrombus. Indeed, there is increasing evidence that intraluminal thrombus in abdominal aortic aneurysms is biologically active and should not be treated as homogeneous inert material. In this review paper, we bring together diverse findings from the literature to encourage next generation models that account for the biochemomechanics of growth and remodeling in patient-specific, thrombus-laden abdominal aortic aneurysms.
Abdominal aortic aneurysms (AAAs) typically develop an intraluminal thrombus (ILT), yet most computational models of AAAs have focused on either the mechanics of the wall or the hemodynamics within the lesion, both in the absence of ILT. In the few cases wherein ILT has been modeled directly, as, for example, in static models that focus on the state of stress in the aortic wall and the associated rupture risk, thrombus has been modeled as an inert, homogeneous, load-bearing material. Given the biochemomechanical complexity of an ILT, there is a pressing need to consider its diverse effects on the evolving aneurysmal wall. Herein, we present the first growth and remodeling model that addresses together the biomechanics, mechanobiology, and biochemistry of thrombus-laden AAAs. Whereas it has been shown that aneurysmal enlargement in the absence of ILT depends primarily on the stiffness and turnover of fibrillar collagen, we show that the presence of a thrombus within lesions having otherwise the same initial wall composition and properties can lead to either arrest or rupture depending on the biochemical effects (e.g., release of proteases) and biomechanical properties (e.g., stiffness of fibrin) of the ILT. These computational results suggest that ILT should be accounted for when predicting the potential enlargement or rupture risk of AAAs and highlight specific needs for further experimental and computational research.
Abdominal aortic aneurysms (AAAs) typically harbour an intraluminal thrombus (ILT), yet most prior computational models neglect biochemomechanical effects of thrombus on lesion evolution. We recently proposed a growth and remodelling model of thrombus-laden AAAs that introduced a number of new constitutive relations and associated model parameters. Because values of several of these parameters have yet to be elucidated by clinical data, and could vary significantly from patient to patient, the aim of this study was to investigate the possible extent to which these parameters influence AAA evolution. Given that some of these parameters model potential effects of factors that influence the risk of rupture, this study also provides insight into possible roles of common risk factors on the natural history of AAAs. Despite geometrical limitations of a cylindrical domain, findings support current thought that smoking, hypertension, and female sex likely increase the risk of rupture. Although thrombus thickness is not a reliable risk factor for rupture, the model suggests that the presence of ILT may have a destabilizing effect on AAA evolution, consistent with histological findings from human samples. Finally, simulations support two hypotheses that should be tested on patient-specific geometries in the future. First, ILT is a potential source of the staccato enlargement observed in many AAAs. Second, ILT can influence rupture risk, positively or negatively, via competing biomechanical (e.g., stress shielding) and biochemical (i.e., proteolytic) effects. Although further computational and experimental studies are needed, the present findings highlight the importance of considering ILT when predicting aneurysmal enlargement and rupture risk.
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