title: Mechanobiological stability: a new paradigm to understand the enlargement of aneurysms?
abstract: Static and dynamic mechanical instabilities were previously suggested, and then rejected, as mediators of aneurysmal development, which leaves open the question of the underlying mechanism. In this paper, we suggest as a new paradigm the interpretation of aneurysms as mechanobiological instabilities. For illustrative purposes, we compare analytical calculations with computational simulations of the growth and remodelling of idealized fusiform abdominal aortic aneurysms and experimental and clinical findings. We show that the concept of mechanobiological stability is consistent with the impact of risk factors such as age, smoking or diabetes on the initiation and enlargement of these lesions as well as adaptive processes in the healthy abdominal aorta such as dilatation during ageing or in hypertension. In general, high stiffness, an increased capacity for stress-mediated matrix production, and slow matrix turnover all improve the mechanobiological stability of blood vessels. This theoretical understanding may help guide prognosis and the development of future therapies for aneurysms as it enables systematic ways to attenuate enlargement.
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA christian.cyron@yale.edu.
authors.forename: C J
authors.initials: CJ
authors.lastname: Cyron
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
authors.forename: J 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 School of Medicine, New Haven, CT, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Humphrey
mesh_terms: D000375:Aging / Q000378:metabolism / Q000473:pathology; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D003920:Diabetes Mellitus / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008955:Models, Cardiovascular; D012907:Smoking / Q000009:adverse effects / Q000378:metabolism / Q000503:physiopathology
keywords: Lyapunov stability; collagen; growth and remodelling; matrix turnover; pathogenesis