Carotid Plaque Vulnerability

Cicha, Iwona; Wörner, Anja; Urschel, Katharina; Beronov, Kamen N.; Goppelt‐Struebe, Margarete; Verhoeven, Eric L.G.; Daniel, Werner G.; Garlichs, Christoph D.

doi:10.1161/strokeaha.111.627265

Cited by 88 publications

(53 citation statements)

References 41 publications

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“…Because the cap stress, which is a potential physical factor that contributes to plaque rupture, increased as the asymmetry increased, we suspect that asymmetric plaque geometry could increase the danger of plaque rupture. This observation also agreed with clinical findings that upstream ruptured plaques exhibited a strongly pronounced longitudinal asymmetry (Cicha et al, 2011 Fig. 4 Equivalent stress contour in the longitudinal cross section at peak pressure (the arrow head denotes max stress location).The maximum cap stress increased as the asymmetry increased, and the location of it moved to the proximal cap for the asymmetric models.…”

Section: Resultssupporting

confidence: 86%

Effects of longitudinal asymmetric distribution of a lipid core on plaque wall stress

Chhai

Lee

Rhee

2017

JBSE

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Effects of longitudinal asymmetric distribution of a lipid core on plaque wall stress IntroductionAtherosclerotic plaque rupture contributes to acute coronary syndrome, one of the leading causes of death in the world. It is composed of lipid rich necrotic cores and calcium deposits enclosed by a protective fibrous cap, which is a thin fibrous tissue between the lumen of the blood vessel and the lipid core. If the fibrous cap is disrupted, a cascade of events that include thrombosis, coronary occlusion, and subsequent myocardial infarction could occur (Libby, 2013). Studies have shown that the mechanical stress and structural integrity of the wall tissues of the plaque determine its susceptibility to disruption.Two different types of stresses act on the plaque tissues: circumferential tensile wall stress, which is caused by pulsating blood pressure, and luminal wall shear stress, which is caused by blood flow. Because tensional wall stress is several orders of magnitude higher than wall shear stress exerted by blood flow (Salger et al., 2005), plaque rupture has been attributed to circumferential wall stress (Ohayon et al., 2005), which is influenced by the morphology and mechanical properties of the plaque. It has been shown that atherosclerotic plaques with large plaque burdens (defined as the plaque area over the vessel area at the cross section) and thin cap thicknesses (less than 65 μm) are more vulnerable (Burke et al. 1997). Computational stress analysis has been performed in order to estimate the plaque wall stress using the idealized plaque models (Ohayon et al. 2008, Akyildiz et al., 2011, Zareh et al., 2015. Recently, three dimensional patient specific plaque models have been reconstructed from diagnostic medical images such as ultrasound, OCT, and MRI images for stress analysis (Nieuwstadt et al., 2013, Kelly-Arnold et al., 2013, Wang et al., 2015 and computational analysis has been performed. They provide a more realistic geometry for wall stress and flow analyses, but they are not ideally suited for obtaining accurate plaque wall morphology due to limitations that include Pengsrorn CHHAI*, Jin Hyun LEE* and Kyehan RHEE* *Department of Mechanical Engineering, Myongji University 38-2 Namdong, Cheoin-gu, Yongin, Gyeonggi-do 449-728, Republic of Korea E-mail: khanrhee@mju.ac.kr AbstractThe rupture of the atherosclerotic plaque is related to the mechanical stress and structural integrity of plaque wall tissues. In order to investigate the longitudinal asymmetry across the stenosis of the arterial plaque wall, asymmetric plaque wall models were constructed by skewing the lipid core distribution in the upstream direction. Wall stress and blood flow in the coronary artery models were computationally analyzed considering fluid and structure interaction. The values of maximum cap stress increased, and its location moved toward the proximal cap as asymmetry increased. Hemodynamic wall shear stress (WSS) did not change much owing to negligible changes in luminal geometry, but the maximum WSS and the spatial gra...

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Section: Resultssupporting

confidence: 86%

Effects of longitudinal asymmetric distribution of a lipid core on plaque wall stress

Chhai

Lee

Rhee

2017

JBSE

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“…This finding suggests that the distribution of vessel density toward upstream regions is not just a feature exclusive for more advanced, late stage plaques. Ruptures in atherosclerotic plaques are most commonly found in the upstream region[4–7] and previous cross-sectional studies reported increased contrast agent uptake in carotid plaques from patients with previous ischemic stroke[15, 22, 24, 25]. In the current study, the distribution of contrast agent uptake between upstream and downstream parts of the plaque in patients with previous ipsilateral symptoms compared with asymptomatic patients was similar.…”

Section: Discussionsupporting

confidence: 71%

“…Different types of shear stress might induce different gene expression patterns in endothelial cells[2], possibly leading to differences in plaque phenotype. In fact, our group and others have shown that the upstream region of the advanced carotid plaque exhibits a more vulnerable phenotype and is often the site of plaque rupture[3–7]. Vascularization of the plaque has been linked to plaque vulnerability and progression, possibly by providing an entry point for inflammatory cells, causing intra-plaque hemorrhage (IPH), inflammation and subsequent destabilization[8–10].…”

Section: Introductionmentioning

confidence: 99%

“…Vascularization of the plaque has been linked to plaque vulnerability and progression, possibly by providing an entry point for inflammatory cells, causing intra-plaque hemorrhage (IPH), inflammation and subsequent destabilization[8–10]. Two studies reported that plaque vascularization was increased in the upstream region[5, 7], but only the shoulder regions of the plaques were studied and the exact relation of the tissue sections to the point maximum stenosis were not reported. Furthermore, those studies relied on ex vivo assessment of endarterectomy specimens from patients with late stage, advanced atherosclerotic disease.…”

Section: Introductionmentioning

confidence: 99%

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Increased Vascularization in the Vulnerable Upstream Regions of Both Early and Advanced Human Carotid Atherosclerosis

et al. 2016

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BackgroundVascularization of atherosclerotic plaques has been linked to plaque vulnerability. The aim of this study was to test if the vascularization was increased in upstream regions of early atherosclerotic carotid plaques and also to test if the same pattern of vascularization was seen in complicated, symptomatic plaques.MethodsWe enrolled 45 subjects with early atherosclerotic lesions for contrast enhanced ultrasound and evaluated the percentage of plaque area in a longitudinal ultrasound section which contained contrast agent. Contrast-agent uptake was evaluated in both the upstream and downstream regions of the plaque. We also collected carotid endarterectomy specimens from 56 subjects and upstream and downstream regions were localized using magnetic resonance angiography and analyzed using histopathology and immunohistochemistry.ResultsVascularization was increased in the upstream regions of early carotid plaques compared with downstream regions (30% vs. 23%, p = 0.033). Vascularization was also increased in the upstream regions of advanced atherosclerotic lesions compared with downstream regions (4.6 vs. 1.4 vessels/mm2, p = 0.001) and was associated with intra-plaque hemorrhage and inflammation.ConclusionsVascularization is increased in the upstream regions of both early and advanced plaques and is in advanced lesions mainly driven by inflammation.

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“…The fibrous cap of a plaque is exposed to the highest strain, and shear stress, at its upstream edge (49). Previous work has shown that macrophage invasion is higher in the upstream edge of plaques (24, 36) and that resident macrophages in the upstream edge increase expression of proteolytic enzymes (24), thereby weakening the plaque. In addition, the fibrous cap on the upstream edge of plaques tends to be more ulcerated and thinner and, when combined with high shear stresses, may lead to destabilization and rupture of the plaque (33, 49).…”

Section: Discussionmentioning

confidence: 99%

Endothelial Mechanosignaling: Does One Sensor Fit All?

Givens

Tzima

2016

Antioxidants & Redox Signaling

139

109

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Significance: Forces are important in the cardiovascular system, acting as regulators of vascular physiology and pathology. Residing at the blood vessel interface, cells (endothelial cell, EC) are constantly exposed to vascular forces, including shear stress. Shear stress is the frictional force exerted by blood flow, and its patterns differ based on vessel geometry and type. These patterns range from uniform laminar flow to nonuniform disturbed flow. Although ECs sense and differentially respond to flow patterns unique to their microenvironment, the mechanisms underlying endothelial mechanosensing remain incompletely understood. Recent Advances: A large body of work suggests that ECs possess many mechanosensors that decorate their apical, junctional, and basal surfaces. These potential mechanosensors sense blood flow, translating physical force into biochemical signaling events. Critical Issues: Understanding the mechanisms by which proposed mechanosensors sense and respond to shear stress requires an integrative approach. It is also critical to understand the role of these mechanosensors not only during embryonic development but also in the different vascular beds in the adult. Possible cross talk and integration of mechanosensing via the various mechanosensors remain a challenge. Future Directions: Determination of the hierarchy of endothelial mechanosensors is critical for future work, as is determination of the extent to which mechanosensors work together to achieve force-dependent signaling. The role and primary sensors of shear stress during development also remain an open question. Finally, integrative approaches must be used to determine absolute mechanosensory function of potential mechanosensors. Antioxid. Redox Signal. 25, 373–388.

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Carotid Plaque Vulnerability

Cited by 88 publications

References 41 publications

Effects of longitudinal asymmetric distribution of a lipid core on plaque wall stress

Effects of longitudinal asymmetric distribution of a lipid core on plaque wall stress

Increased Vascularization in the Vulnerable Upstream Regions of Both Early and Advanced Human Carotid Atherosclerosis

Endothelial Mechanosignaling: Does One Sensor Fit All?

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