Blood vessels are exposed to multiple mechanical forces that are exerted on the vessel wall (radial, circumferential and longitudinal forces) or on the endothelial surface (shear stress). The stresses and strains experienced by arteries influence the initiation of atherosclerotic lesions, which develop at regions of arteries that are exposed to complex blood flow. In addition, plaque progression and eventually plaque rupture is influenced by a complex interaction between biological and mechanical factors-mechanical forces regulate the cellular and molecular composition of plaques and, conversely, the composition of plaques determines their ability to withstand mechanical load. A deeper understanding of these interactions is essential for designing new therapeutic strategies to prevent lesion development and promote plaque stabilization. Moreover, integrating clinical imaging techniques with finite element modelling techniques allows for detailed examination of local morphological and biomechanical characteristics of atherosclerotic lesions that may be of help in prediction of future events. In this ESC Position Paper on biomechanical factors in atherosclerosis, we summarize the current 'state of the art' on the interface between mechanical forces and atherosclerotic plaque biology and identify potential clinical applications and key questions for future research.

Background-In-stent restenosis by excessive intimal hyperplasia reduces the long-term clinical efficacy of coronary stents. Because shear stress (SS) is related to plaque growth in atherosclerosis, we investigated whether variations in SS distribution are related to variations in neointima formation. Methods and Results-In 14 patients, at 6-month follow-up after coronary Wallstent implantation, 3D stent and vessel reconstruction was performed with a combined angiographic and intravascular ultrasound technique (ANGUS). The bare stent reconstruction was used to calculate in-stent SS at implantation, applying computational fluid dynamics

Blood-flow-induced shear stress acting on the arterial wall is of paramount importance in vascular biology. Endothelial cells sense shear stress and largely control its value in a feedback-control loop by adapting the arterial dimensions to blood flow. Nevertheless, to allow for variations in arterial geometry, such as bifurcations, shear stress control is modified at certain eccentrically located sites to let it remain at near-zero levels. In the presence of risk factors for atherosclerosis, low shear stress contributes to local endothelial dysfunction and eccentric plaque build up, but normal-to-high shear stress is atheroprotective. Initially, lumen narrowing is prevented by outward vessel remodeling. Maintenance of a normal lumen and, by consequence, a normal shear stress distribution, however, prolongs local unfavorable low shear stress conditions and aggravates eccentric plaque growth. While undergoing such growth, eccentric plaques at preserved lumen locations experience increased tensile stress at their shoulders making them prone to fissuring and thrombosis. Consequent loss of the plaque-free wall by coverage with thrombus and new tissue may bring shear-stress-controlled lumen preservation to an end. This change causes shear stress to increase, which as a new condition may transform the lesion into a rupture-prone vulnerable plaque. We present a discussion of the role of shear stress, in setting the stage for the generation of rupture-prone, vulnerable plaques, and how this may be prevented.

The heterogeneity of plaque formation, the vascular remodelling response to plaque formation, and the consequent phenotype of plaque instability attest to the extraordinarily complex pathobiology of plaque development and progression, culminating in different clinical coronary syndromes. Atherosclerotic plaques predominantly form in regions of low endothelial shear stress (ESS), whereas regions of moderate/physiological and high ESS are generally protected. Low ESS-induced compensatory expansive remodelling plays an important role in preserving lumen dimensions during plaque progression, but when the expansive remodelling becomes excessive promotes continued influx of lipids into the vessel wall, vulnerable plaque formation and potential precipitation of an acute coronary syndrome. Advanced plaques which start to encroach into the lumen experience high ESS at their most stenotic region, which appears to promote plaque destabilization. This review describes the role of ESS from early atherogenesis to early plaque formation, plaque progression to advanced high-risk stenotic or non-stenotic plaque, and plaque destabilization. The critical implication of the vascular remodelling response to plaque growth is also discussed. Current developments in technology to characterize local ESS and vascular remodelling in vivo may provide a rationale for innovative diagnostic and therapeutic strategies for coronary patients that aim to prevent clinical coronary syndromes.

Background and Purpose-Cerebrovascular events are related to atherosclerotic disease in the carotid arteries and are frequently caused by rupture of a vulnerable plaque. These ruptures are often observed at the upstream region of the plaque, where the wall shear stress (WSS) is considered to be highest. High WSS is known for its influence on many processes affecting tissue regression. Until now, there have been no serial studies showing the relationship between plaque rupture and WSS. Summary of Case-We investigated a serial MRI data set of a 67-year-old woman with a plaque in the carotid artery at baseline and an ulcer at 10-month follow up. The lumen, plaque components (lipid/necrotic core, intraplaque hemorrhage), and ulcer were segmented and the lumen contours at baseline were used for WSS calculation. Correlation of the change in plaque composition with the WSS at baseline showed that the ulcer was generated exclusively at the high WSS location. Conclusions-In this serial MRI study, we found plaque ulceration at the high WSS location of a protruding plaque in the carotid artery. Our data suggest that high WSS influences plaque vulnerability and therefore may become a potential parameter for predicting future events. Key Words: carotid artery Ⅲ MRI Ⅲ shear stress Ⅲ ulceration C erebrovascular events are related to atherosclerotic disease in the carotid arteries and are frequently caused by rupture of a vulnerable plaque. These plaques are characterized by the presence of a large lipid pool covered by a thin fibrous cap with infiltration of macrophages and a scarcity of smooth muscle cells. Plaque rupture has been more frequently observed at the proximal, upstream side of the minimal lumen diameter, 1 which is supposedly exposed to higher wall shear stress (WSS). There is ample evidence that the endothelium responds to high WSS such that it induces antiproliferative action, 2 which may lead to cap thinning. For that reason, we hypothesized that high WSS at the upstream side of the plaque has a biological effect on the fibrous cap and therefore enhances plaque vulnerability. 3 We present a case study in which we demonstrate the relation between high WSS and plaque rupture. Materials and Methods PatientSerial carotid MRI examinations were performed on a 67-year-old individual who was found to have moderate carotid stenosis by duplex ultrasonography. The institutional review committee approved the study and the patient gave informed consent. The patient's baseline MRI showed a plaque in the right carotid artery and the 10-month follow-up MRI showed plaque rupture with an ulcer. 4 MRIThe high-resolution, multisequence MRI protocol at baseline and follow up included 4 sequences: 3-dimensional time of flight, T1, T2, and proton density weightings. The in-plane resolution was 0.3ϫ0.3 mm with a slice thickness of 2 mm. The image segmentation was based on the signal intensities relative to the adjacent sternocleidomastoid muscle. A validated scheme 5 of hyper-, iso-, and hypointense signal intensities from the time of...

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American Heart Association type IV plaques consist of a lipid core covered by a fibrous cap, and develop at locations of eccentric low shear stress. Vascular remodeling initially preserves the lumen diameter while maintaining the low shear stress conditions that encourage plaque growth. When these plaques eventually start to intrude into the lumen, the shear stress in the area surrounding the plaque changes substantially, increasing tensile stress at the plaque shoulders and exacerbating fissuring and thrombosis. Local biologic effects induced by high shear stress can destabilize the cap, particularly on its upstream side, and turn it into a rupture-prone, vulnerable plaque. Tensile stress is the ultimate mechanical factor that precipitates rupture and atherothrombotic complications. The shear-stress-oriented view of plaque rupture has important therapeutic implications. In this review, we discuss the varying mechanobiologic mechanisms in the areas surrounding the plaque that might explain the otherwise paradoxical observations and unexpected outcomes of experimental therapies.

Theme Issue Article Biomechanics in vascular biologyand CVD SummaryAtherosclerotic plaques are found at distinct locations in the arterial system, despite the exposure to systemic risk factors of the entire vascular tree. From the study of arterial bifurcation regions, emerges ample evidence that haemodynamics are involved in the local onset and progression of the atherosclerotic disease. This observed co-localisation of disturbed flow regions and lesion prevalence at geometrically predisposed districts such as arterial bifurcations has led to the formulation of a 'haemodynamic hypothesis', that in this review is grounded to the most current research concerning localising factors of vascular disease. In particular, this review focuses on carotid and coronary bifurcations because of their primary relevance to stroke and heart attack. We highlight reported relationships between atherosclerotic plaque location, progression and composition, and fluid forces at vessel's wall, in particular shear stress and its 'easier-tomeasure' surrogates, i.e. vascular geometric attributes (because geometry shapes the flow) and intravascular flow features (because they mediate disturbed shear stress), in order to give more insight in plaque initiation and destabilisation. Analogous to Virchow's triad for thrombosis, atherosclerosis must be thought of as subject to a triad of, and especially interactions among, haemodynamic forces, systemic risk factors, and the biological response of the wall.