An investigation into the critical role of fibre orientation in the ultimate tensile strength and stiffness of human carotid plaque caps

Johnston, Robert D; Gaul, Robert; Lally, Caitríona

doi:10.1016/j.actbio.2021.02.008

Cited by 26 publications

(41 citation statements)

References 53 publications

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“…The artery wall depends on the various mechanical parameters of each layer for proper function and contractility. Recently, the visualisation of such structures have become increasingly feasible, exemplified by Johnston et al [ 43 ▪▪ ] who – using the small angle light scattering technique – found that collagen fibre alignment in the circumferential direction in the plaque cap plays the most dominant role for determining plaque structural stability. These plaques exhibited superior load bearing (i.e.…”

Section: Collagen Structure and Plaque Integritymentioning

confidence: 99%

Extracellular matrix: paving the way to the newest trends in atherosclerosis

Gialeli

Shami

Gonçalves

2021

Current Opinion in Lipidology

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Purpose of review The extracellular matrix (ECM) is critical for all aspects of vascular pathobiology. In vascular disease the balance of its structural components is shifted. In atherosclerotic plaques there is in fact a dynamic battle between stabilizing and proinflammatory responses. This review explores the most recent strides that have been made to detail the active role of the ECM – and its main binding partners – in driving atherosclerotic plaque development and destabilization. Recent findings Proteoglycans-glycosaminoglycans (PGs-GAGs) synthesis and remodelling, as well as elastin synthesis, cross-linking, degradation and its elastokines potentially affect disease progression, providing multiple steps for potential therapeutic intervention and diagnostic targeted imaging. Of note, GAGs biosynthetic enzymes modulate the phenotype of vascular resident and infiltrating cells. In addition, while plaque collagen structure exerts very palpable effects on its immediate surroundings, a new role for collagen is also emerging on a more systemic level as a biomarker for cardiovascular disease as well as a target for selective drug-delivery. Summary The importance of studying the ECM in atherosclerosis is more and more acknowledged and various systems are being developed to visualize, target and mimic it.

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Section: Collagen Structure and Plaque Integritymentioning

confidence: 99%

Extracellular matrix: paving the way to the newest trends in atherosclerosis

Gialeli

Shami

Gonçalves

2021

Current Opinion in Lipidology

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“…The fibrous cap predominantly consists of fibrillar collagen type I and III [21]- [23] . How collagen fibers are distributed varies throughout and between caps, though Johnston et al suggested that circumferentially orientated collagen fibers in the cap play the most dominant role for determining plaque stability [15], [24] . The strength and stability of these fibers is tightly regulated by intra-and intermolecular cross-links that are generated during collagen maturation.…”

Section: Introductionmentioning

confidence: 99%

Tissue-engineered Collagenous Fibrous Cap Models to Systematically Elucidate Atherosclerotic Plaque Rupture.

Wissing

Heiden

Serra

et al. 2021

Preprint

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A significant amount of vascular thrombotic events is associated with rupture of the fibrous cap that overlie atherosclerotic plaques. Cap rupture is however difficult to predict due to the heterogenous composition of the plaque, unknown material properties, and the stochastic nature of the event. Here, we aim to create tissue engineered human fibrous cap models with a variable but controllable collagen composition, suitable for mechanical testing, to scrutinize the reciprocal relationships between composition and mechanical properties. Myofibroblasts were cultured in 1 x 1.5 cm-sized fibrin-based constrained gels for 21 days according to established (dynamic) culture protocols (i.e. static, intermittent or continuous loading) to vary collagen composition (e.g. amount, type and organization). At day 7, a soft 2 mm ∅ fibrin inclusion was introduced in the centre of each tissue to mimic the soft lipid core, simulating the heterogeneity of a plaque. Results demonstrate reproducible collagenous tissues, that mimic the bulk mechanical properties of human caps and vary in collagen composition due to the presence of an successfully integrated soft inclusion and the culture protocol applied. The models can be deployed to assess tissue mechanics, evolution and failure of fibrous caps or complex heterogeneous tissues in general.

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“…How collagen fibers are distributed varies throughout and between caps, though Johnston et al suggested that circumferentially orientated collagen fibers in the cap play the most dominant role for determining plaque stability. 15,24 The strength and stability of these fibers is tightly regulated by intra- and intermolecular cross-links that are generated during collagen maturation. Lysyl oxidase (LOX) mediated enzymatic crosslinking is one of the main extracellular processing steps that impacts collagen tensile strength and its resistance to proteolytic enzymes.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Various cap strength values are reported in literature, ranging from 158 kPa 36 to 870 kPa 24 . The variability in reported strength values is most probably related to variances in cap composition and loading, affecting the locus of peak mechanical stress and eventual failure mechanism 24 . Correspondingly, several plaque failure mechanisms have been proposed, including delamination 37 , debonding 38 , cavitation 39 , fatigue 40 and failure 35 .…”

Section: Introductionmentioning

confidence: 99%

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Tissue-engineered collagenous fibrous cap models to systematically elucidate atherosclerotic plaque rupture

Wissing

Heiden

Serra

et al. 2021

Preprint

View full text Add to dashboard Cite

A significant amount of vascular thrombotic events is associated with rupture of the fibrous cap that overlie atherosclerotic plaques. Cap rupture is however difficult to predict due to the heterogenous composition of the plaque, unknown material properties, and the stochastic nature of the event. Here, we aim to create tissue engineered human fibrous cap models with a variable but controllable collagen composition, suitable for mechanical testing, to scrutinize the reciprocal relationships between composition and mechanical properties. Myofibroblasts were cultured in 1 x 1.5 cm-sized fibrin-based constrained gels for 21 days according to established (dynamic) culture protocols (i.e. static, intermittent or continuous loading) to vary collagen composition (e.g. amount, type and organization). At day 7, a soft 2 mm diameter fibrin inclusion was introduced in the centre of each tissue to mimic the soft lipid core, simulating the heterogeneity of a plaque. Results demonstrate reproducible collagenous tissues, that mimic the bulk mechanical properties of human caps and vary in collagen composition due to the presence of an successfully integrated soft inclusion and the culture protocol applied. The models can be deployed to assess tissue mechanics, evolution and failure of fibrous caps or complex heterogeneous tissues in general.

show abstract

An investigation into the critical role of fibre orientation in the ultimate tensile strength and stiffness of human carotid plaque caps

Cited by 26 publications

References 53 publications

Extracellular matrix: paving the way to the newest trends in atherosclerosis

Extracellular matrix: paving the way to the newest trends in atherosclerosis

Tissue-engineered Collagenous Fibrous Cap Models to Systematically Elucidate Atherosclerotic Plaque Rupture.

Tissue-engineered collagenous fibrous cap models to systematically elucidate atherosclerotic plaque rupture

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