Size and proximity of micro-scale hard-inclusions increase the risk of rupture in fibroatheroma-like laboratory models

Corti, A; Khalil, Daniel; Paolis, Annalisa De; Cardoso, Luís

doi:10.1016/j.jmbbm.2023.105749

Cited by 3 publications

(5 citation statements)

References 40 publications

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“…Our model serves as a tunable platform in which the interplay between the collagenous matrix and HA particles can be studied, and their role on tissue mechanics can be analyzed. Using our model, we detected that the incorporation of HA particles lowered the UTS, which was also observed in a recent experimental study by the group of Cardoso, 34 where micro-beads were incorporated in a silicone-based model. The reduction in UTS could possibly be explained by a local stress increase at the tensile poles, as described in multiple computational models, which show that microcalcifications can be seen as local stress concentrators, 17,19,35,36 an effect that could be present in our model and was also hypothesized by Cardoso.…”

Section: Discussionsupporting

confidence: 87%

“…The reduction in UTS could possibly be explained by a local stress increase at the tensile poles, as described in multiple computational models, which show that microcalcifications can be seen as local stress concentrators, 17,19,35,36 an effect that could be present in our model and was also hypothesized by Cardoso. 34 However, future research should focus on rupture path analysis to confirm the hypothesis that microcalcifications directly affect cap mechanics and rupture. Another factor to take into consideration with regard to tissue mechanics is the collagenous matrix, since this is the main load-bearing component of the fibrous cap.…”

Section: Discussionmentioning

confidence: 98%

“…However, in computational models, it has been discovered that there are various characteristics of microcalcifications that can influence the local stress accumulations they cause. It was found that they have the most consequential effect depending on their size, 34,41 location, 24 shape, 17,36 and spacing. 35 With regard to size, it has been shown that microcalcifications smaller than 5 μ m should not be biomechanically dangerous.…”

Section: Discussionmentioning

confidence: 99%

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A tissue-engineered model of the atherosclerotic plaque cap: Toward understanding the role of microcalcifications in plaque rupture

Jansen,

Crielaard,

Wissing

et al. 2023

APL Bioengineering

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Rupture of the cap of an atherosclerotic plaque can lead to thrombotic cardiovascular events. It has been suggested, through computational models, that the presence of microcalcifications in the atherosclerotic cap can increase the risk of cap rupture. However, the experimental confirmation of this hypothesis is still lacking. In this study, we have developed a novel tissue-engineered model to mimic the atherosclerotic fibrous cap with microcalcifications and assess the impact of microcalcifications on cap mechanics. First, human carotid plaque caps were analyzed to determine the distribution, size, and density of microcalcifications in real cap tissue. Hydroxyapatite particles with features similar to real cap microcalcifications were used as microcalcification mimics. Injected clusters of hydroxyapatite particles were embedded in a fibrin gel seeded with human myofibroblasts which deposited a native-like collagenous matrix around the particles, during the 21-day culture period. Second harmonic multiphoton microscopy imaging revealed higher local collagen fiber dispersion in regions of hydroxyapatite clusters. Tissue-engineered caps with hydroxyapatite particles demonstrated lower stiffness and ultimate tensile stress than the control group samples under uniaxial tensile loading, suggesting increased rupture risk in atherosclerotic plaques with microcalcifications. This model supports previous computational findings regarding a detrimental role for microcalcifications in cap rupture risk and can further be deployed to elucidate tissue mechanics in pathologies with calcifying soft tissues.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A tissue-engineered model of the atherosclerotic plaque cap: Toward understanding the role of microcalcifications in plaque rupture

Jansen,

Crielaard,

Wissing

et al. 2023

APL Bioengineering

View full text Add to dashboard Cite

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“…Larger beads (diameter > 80 μm) reduced the ultimate tensile stress significantly, while smaller beads (diameter 6 μm) only were of effect in thin (100 μm) experimental samples. Furthermore, higher concentrations of particles correlated with lower stresses at rupture[ 55 ], endorsing the results from numerical models.…”

Section: Cap Components: Role In Cap Mechanicssupporting

confidence: 58%

“…Experimentally, the effect of micro-beads, representing microcalcifications with varying diameters and concentrations, within a silicone-based material has been investigated [ 55 ]. Larger beads (diameter > 80 μm) reduced the ultimate tensile stress significantly, while smaller beads (diameter 6 μm) only were of effect in thin (100 μm) experimental samples.…”

Section: Cap Components: Role In Cap Mechanicsmentioning

confidence: 99%

The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics

Jansen,

Cahalane,

Hengst

et al. 2024

Basic Res Cardiol

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The rupture of an atherosclerotic plaque cap overlying a lipid pool and/or necrotic core can lead to thrombotic cardiovascular events. In essence, the rupture of the plaque cap is a mechanical event, which occurs when the local stress exceeds the local tissue strength. However, due to inter- and intra-cap heterogeneity, the resulting ultimate cap strength varies, causing proper assessment of the plaque at risk of rupture to be lacking. Important players involved in tissue strength include the load-bearing collagenous matrix, macrophages, as major promoters of extracellular matrix degradation, and microcalcifications, deposits that can exacerbate local stress, increasing tissue propensity for rupture. This review summarizes the role of these components individually in tissue mechanics, along with the interplay between them. We argue that to be able to improve risk assessment, a better understanding of the effect of these individual components, as well as their reciprocal relationships on cap mechanics, is required. Finally, we discuss potential future steps, including a holistic multidisciplinary approach, multifactorial 3D in vitro model systems, and advancements in imaging techniques. The obtained knowledge will ultimately serve as input to help diagnose, prevent, and treat atherosclerotic cap rupture.

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Usefulness of the ECORE-BF Scale to Determine Atherogenic Risk in 386,924 Spanish Workers

Marina Arroyo,

Ramírez Gallegos,

López-González

et al. 2024

Nutrients

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Background: Cardiovascular diseases are the leading cause of death worldwide. Obesity and atherosclerosis are considered risk factors for this pathology. There are multiple methods to evaluate obesity, in the same way as there are different formulas to determine atherogenic risk. Since both pathologies are closely related, the objective of our work was to evaluate whether the ECORE-BF scale is capable of predicting atherogenic risk. Methods: Observational, descriptive, and cross-sectional study in which 386,924 workers from several autonomous communities in Spain participated. The association between the ECORE-BF scale and five atherogenic risk indices was evaluated. The relationship between variables was assessed using the chi-square test and Student’s t test in independent samples. Multivariate analysis was performed with the multinomial logistic regression test, calculating the odds ratio and 95% confidence intervals, with the Hosmer–Lemeshow goodness-of-fit test. ROC curves established the cut-off points for moderate and high vascular age and determined the Youden index. Results: The mean values of the ECORE-BF scale were higher in individuals with atherogenic dyslipidemia and the lipid triad, as well as in those with elevated values of the three atherogenic indices studied, with p <0.001 in all cases. As atherogenic risk increased across the five evaluated scales, the prevalence of obesity also significantly increased, with p <0.001 in all cases. In the ROC curve analysis, the AUCs for atherogenic dyslipidemia and the lipid triad were above 0.75, indicating a good association between these scales and the ECORE-BF. Although the Youden indices were not exceedingly high, they were around 0.5. Conclusions: There is a good association between atherogenic risk scales, atherogenic dyslipidemia, and lipid triad, and the ECORE-BF scale. The ECORE-BF scale can be a useful and quick tool to evaluate atherogenic risk in primary care and occupational medicine consultations without the need for blood tests.

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Size and proximity of micro-scale hard-inclusions increase the risk of rupture in fibroatheroma-like laboratory models

Cited by 3 publications

References 40 publications

A tissue-engineered model of the atherosclerotic plaque cap: Toward understanding the role of microcalcifications in plaque rupture

A tissue-engineered model of the atherosclerotic plaque cap: Toward understanding the role of microcalcifications in plaque rupture

The interplay of collagen, macrophages, and microcalcification in atherosclerotic plaque cap rupture mechanics

Usefulness of the ECORE-BF Scale to Determine Atherogenic Risk in 386,924 Spanish Workers

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