Parametric study of effects of collagen turnover on the natural history of abdominal aortic aneurysms.
John S. Wilson,Seungik Baek,Jay D. Humphrey +2 more
TLDR
Assessment of rupture risk could be improved by future experiments that delineate and quantify different aspects of patient-specific collagen turnover and that such understanding could lead to new targeted therapeutics.Abstract:
Abdominal aortic aneurysms (AAAs) are characterized by significant changes in the architecture of the aortic wall, notably, loss of functional elastin and smooth muscle. Because collagen is the principal remaining load-bearing constituent of the aneurysmal wall, its turnover must play a fundamental role in the natural history of the lesion. Nevertheless, detailed investigations of the effects of different aspects of collagen turnover on AAA development are lacking. A finite-element membrane model of the growth and remodelling of idealized AAAs was thus used to investigate parametrically four of the primary aspects of collagen turnover: rates of production, half-life, deposition stretch (prestretch) and material stiffness. The predicted rates of aneurysmal expansion and spatio-temporal changes in wall thickness, biaxial stresses and maximum collagen fibre stretch at the apex of the lesion depended strongly on all four factors, as did the predicted clinical endpoints (i.e. arrest, progressive expansion or rupture). Collagen turnover also affected the axial expansion, largely due to mechanical changes within the shoulder region of the lesion. We submit, therefore, that assessment of rupture risk could be improved by future experiments that delineate and quantify different aspects of patient-specific collagen turnover and that such understanding could lead to new targeted therapeutics.read more
Citations
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Growth and remodeling of load-bearing biological soft tissues
TL;DR: The two primary theoretical approaches for describing mechano-regulated soft tissue growth and remodeling on the continuum level as well as hybrid approaches that attempt to combine the advantages of these two approaches while avoiding their disadvantages are reviewed.
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A haemodynamic predictor of intraluminal thrombus formation in abdominal aortic aneurysms
TL;DR: The need for further consideration of the TFP, or a similar combined metric, as a potentially useful clinical predictor of the possible formation of ILT in AAAs is suggested.
Journal ArticleDOI
A homogenized constrained mixture (and mechanical analog) model for growth and remodeling of soft tissue
TL;DR: This paper presents a temporally homogenized constrained mixture model that combines advantages of both classical approaches, namely a biologically motivated micromechanical foundation, a simple computational implementation, and low computational cost and suggests an intimate relationship between models of growth and remodeling and viscoelasticity.
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Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms
TL;DR: Diverse findings from the literature are brought together to encourage next generation models that account for the biochemomechanics of growth and remodeling in patient-specific, thrombus-laden abdominal aortic aneurysms.
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Differential cell-matrix mechanoadaptations and inflammation drive regional propensities to aortic fibrosis, aneurysm or dissection in hypertension
TL;DR: Early mechanoadaptation of the infrarenal aorta does not preclude subsequent acceleration of neointimal formation, however, and there is a clear need for more systematic assessments of aortic disease progression, not simply a singular focus on a particular region or condition.
References
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Immediate repair compared with surveillance of small abdominal aortic aneurysms.
Frank A. Lederle,Samuel E. Wilson,Gary R. Johnson,Donovan B. Reinke,Fred N. Littooy,Charles W. Acher,David J. Ballard,Louis M. Messina,Ian L. Gordon,Edmund P. Chute,William C. Krupski,Steven J. Busuttil,Gary W. Barone,Steven Sparks,Linda M. Graham,Joseph H. Rapp,Michel S. Makaroun,Gregory L. Moneta,Robert A. Cambria,Raymond G. Makhoul,Darwin Eton,Howard J. Ansel,Julie A. Freischlag,Dennis F. Bandyk +23 more
TL;DR: The rate of death from any cause, the primary outcome, was not significantly different in the two groups (relative risk in the immediate-repair group as compared with the surveillance group), and the rate of repair had been performed in 92.6 percent of the patients in the immediately- Repair group and 61.6% of those in the Surveillance group.
Journal ArticleDOI
Mutations in smooth muscle α-actin ( ACTA2 ) lead to thoracic aortic aneurysms and dissections
Dongchuan Guo,Hariyadarshi Pannu,Van Tran-Fadulu,Christina L. Papke,Robert Yu,Nili Avidan,Scott Bourgeois,Anthony L. Estrera,Hazim J. Safi,Elizabeth Sparks,David J. Amor,Lesley C. Adès,Vivienne McConnell,Colin E. Willoughby,Dianne N. Abuelo,Marcia C. Willing,Richard A. Lewis,Dong H. Kim,Steve Scherer,Poyee P. Tung,Chul Ahn,L. Maximilian Buja,Chander Raman,Sanjay Shete,Dianna M. Milewicz +24 more
TL;DR: It is shown that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (TAAD), and the importance of SMC contraction in maintaining the structural integrity of the ascending aorta is indicated.
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Cyclic Stretching Stimulates Synthesis of Matrix Components by Arterial Smooth Muscle Cells in Vitro
TL;DR: Rabbit aortic medial cells were grown on purified elastin membranes, which were then subjected to repeated elongation and relaxation or to agitation without stretching, which resulted in a two- to fourfold increase in rates of collagen, hyaluronate, and chondroitin 6-sulfate synthesis.
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Abdominal aortic aneurysm expansion: risk factors and time intervals for surveillance.
TL;DR: Baseline diameter was strongly associated with growth, suggesting that AAA growth accelerates as the aneurysm enlarges, and annual surveillance intervals are safe for all AAAs ≤45 mm in diameter.
Journal ArticleDOI
Prediction of rupture risk in abdominal aortic aneurysm during observation: Wall stress versus diameter
TL;DR: For AAAs under observation, peak AAA wall stress seems superior to diameter in differentiating patients who will experience catastrophic outcome, and with proportional hazards analysis, peak wall stress and gender were the only significant independent predictors of rupture.