Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events

Stone, Peter H.; Maehara, Akiko; Coskun, Ahmet U.; Maynard, Charles; Zaromitidou, Marina; Siasos, Gerasimos; Andreou, Ioannis; Fotiadis, Dimitris; Stefanou, Kostas; Papafaklis, Michail I.; Michalis, Lampros K.; Lansky, Alexandra J.; Mintz, Gary S.; Serruys, Patrick W.; Feldman, Charles L.; Stone, Gregg W.

doi:10.1016/j.jcmg.2017.01.031

Cited by 142 publications

(103 citation statements)

References 23 publications

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“…In addition, the CFD simulations and subsequent statistical post-processing indicted that several OCT-defined erosions occurred in regions with modest or no stenosis, where the predominant flow feature was oscillatory shear stress (defined through OSI) [48,49]. Low time averaged wall shear stress or elevated OSI values strongly correlate with the focal predilection sites for atherosclerosis [32,[50][51][52] and tend to activate endothelial cells, priming them for inflammatory activation and apoptosis [28,34,53]. Inducing endothelial apoptosis experimentally can initiate thrombosis [54] supporting a role for apoptosis triggering endothelial erosion.…”

Section: Discussionmentioning

confidence: 95%

“…The haemodynamic environment exquisitely regulates the behaviour of endothelial cells: it modulates metabolism, cell shape, cytoskeleton arrangement, proliferation, permeability, response to inflammatory stimuli and apoptosis [25][26][27][28][29]. Thus, haemodynamics strongly influences plaque development, progression and features of lesions that determine their propensity to rupture [30][31][32][33]. Emerging evidence also supports the involvement of haemodynamics in endothelial erosion.…”

Section: Introductionmentioning

confidence: 98%

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A pivotal role for Nrf2 in endothelial detachment- implications for endothelial erosion of stenotic plaques

Satta

McElroy

Langford-Smith

et al. 2019

Preprint

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Endothelial erosion of atherosclerotic plaques and resulting thrombosis causes approximately 30% of acute coronary syndromes (ACS). As changes in the haemodynamic environment strongly influence endothelial function and contribute to plaque development, we reconstructed the coronary artery geometries of plaques with thrombi overlying intact fibrous caps from 17 ACS patients and performed computational fluid dynamic analysis. The results demonstrated that erosions frequently occur within areas of stenosis exposed to elevated flow. We recapitulated this flow environment in vitro, exposing human coronary artery endothelial cells to elevated flow and modelled smoking (a risk factor for erosion) by exposure to a combination of aqueous cigarette smoke extract and TNFα. This treatment induced endothelial detachment, which increased with pharmacological activation of the antioxidant system controlled by transcription factor Nrf2 (encoded by NFE2L2). The expression of Oxidative Stress Growth INhibitor genes OSGIN1 and OSGIN2 increased under these conditions and also in the aortas of mice exposed to cigarette smoke. Sustained high level expression of OSGIN1+2 resulted in cell cycle arrest, induction of senescence, loss of focal adhesions and actin stress fibres, and dysregulation of autophagy. Overexpression of either Nrf2 or OSGIN1+2 induced cell detachment, which did not depend on apoptosis, and could be partially rescued by inhibition of HSP70 using VER-155008, or AMP kinase activation using metformin. These findings demonstrate that under elevated flow, smokinginduced hyperactivation of Nrf2 can trigger endothelial cell detachment, highlighting a novel mechanism that could contribute to ACS involving endothelial erosion overlying stenotic plaques.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 98%

A pivotal role for Nrf2 in endothelial detachment- implications for endothelial erosion of stenotic plaques

Satta

McElroy

Langford-Smith

et al. 2019

Preprint

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“…These findings are supported by a recent experimental study which showed that high-risk plaques exposed to low ESS are likely to progress to more advanced atherosclerotic lesions,3 and by a serial OCT study which showed that ThCFA/TCFA exposed to low ESS had increased lipid arc and thinner fibrous caps at follow-up 19. In addition, an analysis of the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study showed that low ESS in the shoulders of a vulnerable lesions (ThCFA or TCFA) is associated with future cardiovascular events 20. However, the phenotype of the 3 mm segments located in the shoulders of these lesions was unknown as plaque morphology in this study was defined by the phenotype of the most vulnerable plaque which is more likely to be located at the throat of the stenosis 21.…”

Section: Resultsmentioning

confidence: 99%

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

Bourantas

Zanchin

Sakellarios

et al. 2019

Heart

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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.

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“…The above medications, however, have significant side effects and are associated with an increased cost and thus they should be used only in well-defined high-risk patients. Unlocking the full potential of CTCA imaging in assessing atheroma characteristics and estimating the local haemodynamic forces -which in intravascular imaging studies appear to enable more accurate detection of vulnerable plaques and high-risk patients [3,33] -is essential for the broad use of this modality in the clinical arena. This will allow identification of patients that are likely to sustain a cardiovascular event and benefit from an aggressive treatment of atherosclerosis [34].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Efficacy of Computed Tomographic Coronary Angiography in Assessing Coronary Artery Morphology and Physiology: Rationale and Study Design

et al. 2020

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Computed tomographic coronary angiography (CTCA) is a non-invasive imaging modality, which allows plaque burden and composition assessment and detection of plaque characteristics associated with increased vulnerability. In addition, CTCA-based coronary artery reconstruction enables local haemodynamic forces assessment, which regulate plaque formation and vascular inflammation and prediction of lesions that are prone to progress and cause events. However, the use of CTCA for vulnerable plaque detection in the clinical arena remains limited. To unlock the full potential of CTCA and enable its broad use, further work is needed to develop user-friendly processing tools that will allow fast and Ramasamy et al.

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Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events

Abstract: Local low ESS provides incremental risk stratification of untreated coronary lesions in high-risk patients, beyond measures of PB, MLA, and morphology.

Cited by 142 publications

References 23 publications

A pivotal role for Nrf2 in endothelial detachment- implications for endothelial erosion of stenotic plaques

A pivotal role for Nrf2 in endothelial detachment- implications for endothelial erosion of stenotic plaques

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

Evaluation of the Efficacy of Computed Tomographic Coronary Angiography in Assessing Coronary Artery Morphology and Physiology: Rationale and Study Design

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