title: A Computational Model of Biochemomechanical Effects of Intraluminal Thrombus on the Enlargement of Abdominal Aortic Aneurysms.
abstract: 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.
authors.affiliation: Faculty of Mechanical Engineering and Naval Architecture, University of Zagreb, Zagreb, Croatia.
authors.forename: Lana
authors.initials: L
authors.lastname: Virag
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Wilson
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.|Vascular Biology and Therapeutics Program, Yale University, New Haven, CT, USA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Humphrey
authors.affiliation: Faculty of Mechanical Engineering and Naval Architecture, University of Zagreb, Zagreb, Croatia.
authors.forename: Igor
authors.initials: I
authors.lastname: Karšaj
mesh_terms: D001012:Aorta, Abdominal / Q000378:metabolism / Q000503:physiopathology; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism / Q000503:physiopathology; D001696:Biomechanical Phenomena; D017364:Collagenases / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D008955:Models, Cardiovascular; D010196:Pancreatic Elastase / Q000378:metabolism; D013314:Stress, Mechanical; D013927:Thrombosis / Q000378:metabolism / Q000503:physiopathology
chemical_list: D005337:Fibrin; D010196:Pancreatic Elastase; D005341:Fibrinolysin; D017364:Collagenases
keywords: Collagen remodeling; Elastin degradation; Growth and remodeling; Proteolytic activity; Wall stress