Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in
            <i>D374Y</i>
            -PCSK9 Hypercholesterolemic Minipigs

Pedrigi, Ryan M.; Poulsen, Christian Bo; Mehta, Vikram V.; Holm, Niels Ramsing; Pareek, Nilesh; Post, Anouk L.; Kılıç, İsmail Doğu; Banya, Winston; Dall’Ara, Gianni; Mattesini, Alessio; Björklund, Martin; Andersen, Niels Peter; Grøndal, Anna K.; Petretto, Enrico; Foin, Nicolas; Davies, Justin E.; Mario, Carlo Di; Bentzon, Jacob F.; Bøtker, Hans Erik; Falk, Erling; Krams, Rob; Silva, Ranil de

doi:10.1161/circulationaha.115.016270

Cited by 63 publications

(51 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Because it does not account for flow reversal, it complements the OSI. This metric has recently been shown to correlate well with local regions of naturally occurring early plaques in the aorta of a rabbit model [36] and initiation of advanced plaques in pigs [1]. LSI and HSI quantify the degree of atherogenic low and high WSS, respectively, using a threshold determined by a non-diseased vessel (herein, we used the contralateral control artery within each mouse).…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, these metrics quantify low and high WSS over a continuous scale compared with a binary approach used by previous studies [6,19]. These metrics have recently been introduced by us in a previous study where they showed good spatial overlap with advanced plaques, including thin cap fibroatheroma (TCFA), in hypercholesterolemic pigs [1]. Together with the results of this study, these metrics also demonstrate the advantage of scale invariance, where they can be used in animals of different sizes including humans.…”

Section: Discussionmentioning

confidence: 99%

“…These metrics include the wall shear stress angle deviation (SAD; a metric of the spatial change in flow direction) [24], relative residence time (RRT; a metric of species transport) [25], oscillatory shear index (OSI; a metric of flow reversal) [26] and the recently developed transverse wall shear stress (tSS; a metric of flow multidirectionality) [27,28]. In addition to these established metrics, we developed two new WSS metrics, the low shear index (LSI) and the high shear index (HSI) [1], which quantify changes in time-averaged WSS (TAWSS) magnitude on a continuous scale. They are formulated as

LSI = \frac{{TAWSS}_{normalLowThresh} - TAWS S_{normalInstrumented}}{TAWS S_{normalLowThresh}},

where

TAWS S_{normalLowThresh} = e^{[\overset{false¯}{\ln (normalTAWS {normalS}_{Control})} - 0.67 \cdot normalSD (\ln (normalTAWS {normalS}_{Control}))]}

and

HSI = \frac{TAWS S_{normalInstrumented} - TAWS S_{normalHighThresh}}{TAWS S_{normalInstrumented}},

where

TAWS S_{normalHighThresh} = e^{[\overset{false¯}{\ln normalTAWS {normalS}_{Control}} + 0.67 \cdot normalSD (\ln (normalTAWS {normalS}_{Control <...>}}

…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Influence of shear stress magnitude and direction on atherosclerotic plaque composition

et al. 2016

Self Cite

View full text Add to dashboard Cite

The precise flow characteristics that promote different atherosclerotic plaque types remain unclear. We previously developed a blood flow-modifying cuff for ApoE−/− mice that induces the development of advanced plaques with vulnerable and stable features upstream and downstream of the cuff, respectively. Herein, we sought to test the hypothesis that changes in flow magnitude promote formation of the upstream (vulnerable) plaque, whereas altered flow direction is important for development of the downstream (stable) plaque. We instrumented ApoE−/− mice (n = 7) with a cuff around the left carotid artery and imaged them with micro-CT (39.6 µm resolution) eight to nine weeks after cuff placement. Computational fluid dynamics was then performed to compute six metrics that describe different aspects of atherogenic flow in terms of wall shear stress magnitude and/or direction. In a subset of four imaged animals, we performed histology to confirm the presence of advanced plaques and measure plaque length in each segment. Relative to the control artery, the region upstream of the cuff exhibited changes in shear stress magnitude only (p < 0.05), whereas the region downstream of the cuff exhibited changes in shear stress magnitude and direction (p < 0.05). These data suggest that shear stress magnitude contributes to the formation of advanced plaques with a vulnerable phenotype, whereas variations in both magnitude and direction promote the formation of plaques with stable features.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LSI = \frac{{TAWSS}_{normalLowThresh} - TAWS S_{normalInstrumented}}{TAWS S_{normalLowThresh}},

where

TAWS S_{normalLowThresh} = e^{[\overset{false¯}{\ln (normalTAWS {normalS}_{Control})} - 0.67 \cdot normalSD (\ln (normalTAWS {normalS}_{Control}))]}

and

HSI = \frac{TAWS S_{normalInstrumented} - TAWS S_{normalHighThresh}}{TAWS S_{normalInstrumented}},

where

TAWS S_{normalHighThresh} = e^{[\overset{false¯}{\ln normalTAWS {normalS}_{Control}} + 0.67 \cdot normalSD (\ln (normalTAWS {normalS}_{Control <...>}}

…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Influence of shear stress magnitude and direction on atherosclerotic plaque composition

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, coronary reconstruction was performed using a methodology that did not include side branches which appear to affect ESS distribution 24. In addition, we assumed a steady and not a pulsatile flow profile; this may allow accurate estimation of the averaged ESS but it cannot assess the role of oscillating ESS on atherosclerotic evolution 25. Finally, the present study, which is the largest serial multimodality imaging study investigating the effect of ESS on plaque morphology, included only a subset of the patients recruited in the IBIS-4 study that included patients admitted with a myocardial infarction who received aggressive treatment with Rosuvastatin, a medication that influences plaque evolution; therefore, the reported results should be interpreted with caution as it is likely to not reflect plaque evolution in other populations.…”

Section: Resultsmentioning

confidence: 99%

Implications of the local haemodynamic forces on the phenotype of coronary plaques

Bourantas

Zanchin

Sakellarios

et al. 2019

Heart

View full text Add to dashboard Cite

AimTo examine the effect of endothelial shear stress (ESS) on the dynamic changes in plaque phenotype.MethodsPatients with myocardial infarction that had intravascular ultrasound-virtual histology (IVUS-VH) and optical coherence tomography (OCT) at baseline and 13-month follow-up were studied. The IVUS-VH data were used to reconstruct the nonculprit vessels, and in the obtained models the ESS was estimated in 3 mm segments. Plaque morphology was derived in each segment from IVUS-VH and OCT. Disease progression was defined as the presence of ≥2 out of the following criteria: reduction in lumen area, increase in plaque burden and change of plaque morphology to a more vulnerable phenotype. Linear mixed effects models were used to assess the effect of ESS in different phenotypes.ResultsSixty-eight vessels were included in the analysis. Low ESS was associated with plaque progression in all phenotypes. The effect of ESS on plaque burden (p for interaction=0.467) and phenotype (p for interaction=0.188) was similar in all plaque types, whereas the effect of ESS on the changes in lumen dimensions was more prominent in disease-free (β=0.70, p<0.001) than fibrotic/fibrocalcific (β=0.28, p<0.001) or lipid-rich plaques (β=0.15, p=0.015). Standalone IVUS-VH misclassified plaque morphology in one-third of the cases leading to erroneous estimations about the effect of ESS on plaque evolution in different phenotypes.ConclusionsThe effect of ESS on plaque progression is similar in all phenotypes and cannot be accurately assessed by standalone IVUS-VH which often misclassifies plaque morphology. Therefore, multimodality imaging should be considered to examine the implications of ESS on plaque evolution.Clinical trial registrationNCT00962416; Post-results.

show abstract

“…A number of clinical and experimental studies using 3D imaging have shown that low shear stress is an important factor in the development of vulnerable plaques. 40,41 In the future, 3D models using 3D printing can provide more accurate models for the study of pathophysiology and assist in evaluating optimal interventional techniques for a patient. 42 …”

Section: Emergence Of Intravascular Imaging and Physiology Assessmentmentioning

confidence: 99%

Interventional Cardiology

Faxon

Williams

2016

Circulation

View full text Add to dashboard Cite

Inducing Persistent Flow Disturbances Accelerates Atherogenesis and Promotes Thin Cap Fibroatheroma Development in D374Y -PCSK9 Hypercholesterolemic Minipigs

Cited by 63 publications

References 38 publications

Influence of shear stress magnitude and direction on atherosclerotic plaque composition

Influence of shear stress magnitude and direction on atherosclerotic plaque composition

Implications of the local haemodynamic forces on the phenotype of coronary plaques

Interventional Cardiology

Contact Info

Product

Resources

About