Protease activity in the multi-layered intra-luminal thrombus of abdominal aortic aneurysms

Folkesson, Maggie; Silveira, Angela; Eriksson, Per; Swedenborg, Jesper

doi:10.1016/j.atherosclerosis.2011.05.002

Cited by 59 publications

(66 citation statements)

References 135 publications

(154 reference statements)

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“…Indeed, aneurysmal walls covered by a thin (1.0 cm) thrombus have significantly higher levels of LE activity, concentrations of active MMP-9 and total MMP-8, and ratios of active MMP-9/ TIMP-1 than those covered by a thick (2.5 cm) thrombus [52]. MMP-9 and LE concentrations are also higher in luminal layers compared with deeper layers, and a significant negative correlation exists between the concentration and activity of LE in the abluminal layer and ILT volume, suggesting that LE may not penetrate well a thick ILT [56]. Of note, the slightly alkaline environment in the aneurysmal wall next to a thin ILT may also accelerate local degradation by elastase [52].…”

Section: Luminal Ilt-aortic Interactionsmentioning

confidence: 81%

“…Notably, a significant correlation has been observed between LE and MMP-9 when compared within the luminal, as well as abluminal, layer [56]. While MMP-9 can be inhibited by TIMP-1, neutrophils can upregulate MMP-9 activity by releasing NGAL, which binds MMP-9 and prevents its inactivation [48].…”

Section: Prominent Role Of the Luminal Layer In Ilt Activitymentioning

confidence: 95%

“…Both of these MMPs, along with MMP-2, are elevated in AAAs, while the MMP inhibitors TIMP-1 and -2 are decreased [52,55]. Nevertheless, both TIMP-1, released from platelet agranules [55], and the elastase inhibitor a1-antitypsin (a1-AT) exist in the luminal layer, potentially explaining (along with latency of the proform of the enzymes) some reports of high MMP-9 and elastase levels in the luminal layer but low activity [56]. Indeed, a negative gradient of latent MMP-9 but positive gradient of active MMP-9 has been reported from luminal to abluminal layers of ILT [37].…”

Section: Prominent Role Of the Luminal Layer In Ilt Activitymentioning

confidence: 99%

“…As a result, measurements of proteolytic activity in these layers may potentially vary in time and space as well as from patient to patient, depending on past and current fibrinolytic activity. For example, Folkesson et al [56] found abluminal proteases to be predominately inactive whereas Fontaine et al [37] reported active MMP-9 at the liquid interface between the ILT and wall.…”

Section: Medial and Abluminal Layersmentioning

confidence: 99%

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Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms

Wilson

Virag

Achille

et al. 2013

Journal of Biomechanical Engineering

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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.

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Section: Luminal Ilt-aortic Interactionsmentioning

confidence: 81%

Section: Prominent Role Of the Luminal Layer In Ilt Activitymentioning

confidence: 95%

Section: Prominent Role Of the Luminal Layer In Ilt Activitymentioning

confidence: 99%

Section: Medial and Abluminal Layersmentioning

confidence: 99%

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Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms

Wilson

Virag

Achille

et al. 2013

Journal of Biomechanical Engineering

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“…27 Together, these detrimental effects may tilt the balance from aneurysm wall cicatrization to wall destruction which promotes growth and eventual rupture.…”

Section: Aneurysm Growth and Rupturementioning

confidence: 99%

Loss of Mural Cells Leads to Wall Degeneration, Aneurysm Growth, and Eventual Rupture in a Rat Aneurysm Model

Marbacher

Marjamaa

Bradacova

et al. 2014

Stroke

105

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Background and Purpose— The biological mechanisms predisposing intracranial saccular aneurysms to growth and rupture are not yet fully understood. Mural cell loss is a histological hallmark of ruptured cerebral aneurysms. It remains unclear whether mural cell loss predisposes to aneurysm growth and eventual rupture. Methods— Sodium dodecyl sulfate decellularized and nondecellularized saccular aneurysm from syngeneic thoracic aortas were transplanted to the abdominal aorta of Wistar rats. Aneurysm patency and growth was followed up for 1 month with contrast-enhanced serial magnetic resonance angiographies. Endoscopy and histology of the aneurysms were used to assess the role of periadventitial environment, aneurysm wall, and thrombus remodeling. Results— Nondecellularized aneurysms (n=12) showed a linear course of thrombosis and remained stable. Decellularized aneurysms (n=12) exhibited a heterogeneous pattern of thrombosis, thrombus recanalization, and growth. Three of the growing aneurysms (n=5) ruptured during the observation period. Growing and ruptured aneurysms demonstrated marked adventitial fibrosis and inflammation, complete wall disruption, and increased neutrophil accumulation in unorganized intraluminal thrombus. Conclusions— In the presented experimental setting, complete loss of mural cells acts as a driving force for aneurysm growth and rupture. The findings suggest that aneurysms missing mural cells are incapable to organize a luminal thrombus, leading to recanalization, increased inflammatory reaction, severe wall degeneration, and eventual rupture.

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A quarter of a century biomechanical rupture risk assessment of abdominal aortic aneurysms. Achievements, clinical relevance, and ongoing developments

Gasser

Miller

Polzer

et al. 2022

Numer Methods Biomed Eng

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Abdominal aortic aneurysm (AAA) disease, the local enlargement of the infrarenal aorta, is a serious condition that causes many deaths, especially in men exceeding 65 years of age. Over the past quarter of a century, computational biomechanical models have been developed towards the assessment of AAA risk of rupture, technology that is now on the verge of being integrated within the clinical decision-making process. The modeling of AAA requires a holistic understanding of the clinical problem, in order to set appropriate modeling assumptions and to draw sound conclusions from the simulation results. In this article we summarize and critically discuss the proposed modeling approaches and report the outcome of clinical validation studies for a number of biomechanics-based rupture risk indices. Whilst most of the aspects concerning computational mechanics have already been settled, it is the exploration of the failure properties of the AAA wall and the acquisition of robust input data for simulations that has the greatest potential for the further improvement of this technology. K E Y W O R D Sabdominal aortic aneurysm, modeling, ruptuer risk assessment, vascular biomechanics | WHAT IS AAAWhilst an aneurysm, a permanent local enlargement of an artery by more than 50% of its diameter, may affect all arteries, the infrarenal aorta is most vulnerable to this disease and often leads to the development of an abdominal aortic aneurysm (AAA). The formation of AAAs is promoted by factors such as old age, male gender, smoking, and high mean arterial pressure (MAP). Furthermore, it is over-represented in persons with a family history of AAA and patients with coronary heart disease and Chronic Obstructive Pulmonary Disease. Aortic aneurysms can also present in patients with rare genetic diseases, such as Ehlers-Danlos syndrome type IV, Marfan syndrome, Loeys-Dietz syndrome, and fibromuscular dysplasia. Most AAAs remain small and therefore do not necessitate clinical intervention. However, an aneurysm may grow to a size that could result in aortic rupture, a life-threatening event. In urban areas only 50% of

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Protease activity in the multi-layered intra-luminal thrombus of abdominal aortic aneurysms

Cited by 59 publications

References 135 publications

Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms

Biochemomechanics of Intraluminal Thrombus in Abdominal Aortic Aneurysms

Loss of Mural Cells Leads to Wall Degeneration, Aneurysm Growth, and Eventual Rupture in a Rat Aneurysm Model

A quarter of a century biomechanical rupture risk assessment of abdominal aortic aneurysms. Achievements, clinical relevance, and ongoing developments

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