The role of structural polymorphism in driving the mechanical performance of the alzheimer's beta amyloid fibrils

Alzheimer's Disease (AD) is related with the abnormal aggregation of amyloid β-peptides Aβ1-40 and Aβ1-42, the latter having a polymorphic character which gives rise to U- or S-shaped fibrils. Elucidating the role played by the nanoscale-material architecture on the amyloid fibril stability is a crucial breakthrough to better understand the pathological nature of amyloid structures and to support the rational design of bio-inspired materials. The computational study here presented highlights the superior mechanical behavior of the S-architecture, characterized by a Young's modulus markedly higher than the U-shaped architecture. The S-architecture showed a higher mechanical resistance to the enforced deformation along the fibril axis, consequence of a better interchain hydrogen bonds' distribution. In conclusion, this study, focusing the attention on the pivotal multiscale relationship between molecular phenomena and material properties, suggests the S-shaped Aβ1-42 species as a target of election in computational screen/design/optimization of effective aggregation modulators

On the association between helical flow and plaque progression in coronary arteries

Arterial hemodynamics is markedly characterized by the presence of helical flow (HF) patterns, whose physiological significance has been investigated in recent years, in particular with respect to the atheroprotective role played by specific HF structures. However, a gap in knowledge still exist on the significance of HF in coronary arteries, a prominent site of atherosclerotic plaque formation. The aim of this study is to carry out, in a representative sample of 15 swine coronary arteries, a systematic analysis of HF and wall thickness using computational fluid dynamics and intravascular ultrasound imaging. In detail, here we investigate possible associations of HF with (1) atherogenic wall shear stress (WSS) phenotypes, and (2) atherosclerotic plaque progression (in a follow up study). Our findings demonstrate for the first time that: (1) HF naturally characterizes coronary hemodynamics; (2) unfavourable conditions of WSS are strongly inversely associated with helicity intensity; (3) HF intensity protects against atherosclerotic plaque growth

Combining 4D Flow MRI and Complex Networks Theory to Characterize the Hemodynamic Heterogeneity in Dilated and Non-dilated Human Ascending Aortas

Motivated by the evidence that the onset and progression of the aneurysm of the ascending aorta (AAo) is intertwined with an adverse hemodynamic environment, the present study characterized in vivo the hemodynamic spatiotemporal complexity and organization in human aortas, with and without dilated AAo, exploring the relations with clinically relevant hemodynamic and geometric parameters. The Complex Networks (CNs) theory was applied for the first time to 4D flow magnetic resonance imaging (MRI) velocity data of ten patients, five of them presenting with AAo dilation. The time-histories along the cardiac cycle of velocity-based quantities were used to build correlation-based CNs. The CNs approach succeeded in capturing large-scale coherent flow features, delimiting flow separation and recirculation regions. CNs metrics highlighted that an increasing AAo dilation (expressed in terms of the ratio between the maximum AAo and aortic root diameter) disrupts the correlation in forward flow reducing the correlation persistence length, while preserving the spatiotemporal homogeneity of secondary flows. The application of CNs to in vivo 4D MRI data holds promise for a mechanistic understanding of the spatiotemporal complexity and organization of aortic flows, opening possibilities for the integration of in vivo quantitative hemodynamic information into risk stratification and classification criteria

Exploring wall shear stress spatiotemporal heterogeneity in coronary arteries combining correlation-based analysis and complex networks with computational hemodynamics

Atherosclerosis at the early stage in coronary arteries has been associated with low cycle-average wall shear stress magnitude. However, parallel to the identification of an established active role for low wall shear stress in the onset/progression of the atherosclerotic disease, a weak association between lesions localization and low/oscillatory wall shear stress has been observed. In the attempt to fully identify the wall shear stress phenotype triggering early atherosclerosis in coronary arteries, this exploratory study aims at enriching the characterization of wall shear stress emerging features combining correlation-based analysis and complex networks theory with computational hemodynamics. The final goal is the characterization of the spatiotemporal and topological heterogeneity of wall shear stress waveforms along the cardiac cycle. In detail, here time-histories of wall shear stress magnitude and wall shear stress projection along the main flow direction and orthogonal to it (a measure of wall shear stress multidirectionality) are analyzed in a representative dataset of 10 left anterior descending pig coronary artery computational hemodynamics models. Among the main findings, we report that the proposed analysis quantitatively demonstrates that the model-specific inlet flow-rate shapes wall shear stress time-histories. Moreover, it emerges that a combined effect of low wall shear stress magnitude and of the shape of the wall shear stress–based descriptors time-histories could trigger atherosclerosis at its earliest stage. The findings of this work suggest for new experiments to provide a clearer determination of the wall shear stress phenotype which is at the basis of the so-called arterial hemodynamic risk hypothesis in coronary arteries

The Atheroprotective Nature of Helical Flow in Coronary Arteries

Arterial hemodynamics is markedly characterized by the presence of helical flow patterns. Previous observations suggest that arterial helical blood flow is of physiological significance, and that its quantitative analysis holds promise for clinical applications. In particular, it has been reported that distinguishable helical flow patterns are potentially atheroprotective in the carotid bifurcation as they suppress flow disturbances. In this context, there is a knowledge gap about the physiological significance of helical flow in coronary arteries, a prominent site of atherosclerotic plaque formation. This study aimed at the quantitative assessment of helical blood flow in coronary arteries, and to investigate its possible associations with vascular geometry and with atherogenic wall shear stress (WSS) phenotypes in a representative sample of 30 swine coronary arteries. This study demonstrates that in coronary arteries: (1) the hemodynamics is characterized by counter-rotating bi-helical flow structures; (2) unfavorable conditions of WSS are strongly and inversely associated with helicity intensity (r=-0.91; p<0.001), suggesting an atheroprotective role for helical flow in the coronary tree; (3) vascular torsion dictates helical flow features (r=0.64; p<0.001). The findings of this work support future studies on the role of helical flow in atherogenesis in coronary arteries

Predicting Lipid-Rich Plaque Progression in Coronary Arteries Using Multimodal Imaging and Wall Shear Stress Signatures

BACKGROUND:Plaque composition and wall shear stress (WSS) magnitude act as well-established players in coronary plaque progression. However, WSS magnitude per se does not completely capture the mechanical stimulus to which the endothelium is subjected, since endothelial cells experience changes in the WSS spatiotemporal configuration on the luminal surface. This study explores WSS profile and lipid content signatures of plaque progression to identify novel biomarkers of coronary atherosclerosis. METHODS: Thirty-seven patients with acute coronary syndrome underwent coronary computed tomography angiography, near-infrared spectroscopy intravascular ultrasound, and optical coherence tomography of at least 1 nonculprit vessel at baseline and 1-year follow-up. Baseline coronary artery geometries were reconstructed from intravascular ultrasound and coronary computed tomography angiography and combined with flow information to perform computational fluid dynamics simulations to assess the time-averaged WSS magnitude (TAWSS) and the variability in the contraction/expansion action exerted by WSS on the endothelium, quantifiable in terms of topological shear variation index (TSVI). Plaque progression was measured as intravascular ultrasound-derived percentage plaque atheroma volume change at 1-year follow-up. Plaque composition information was extracted from near-infrared spectroscopy and optical coherence tomography.RESULTS:Exposure to high TSVI and low TAWSS was associated with higher plaque progression (4.00±0.69% and 3.60±0.62%, respectively). Plaque composition acted synergistically with TSVI or TAWSS, resulting in the highest plaque progression (≥5.90%) at locations where lipid-rich plaque is exposed to high TSVI or low TAWSS. CONCLUSIONS: Luminal exposure to high TSVI, solely or combined with a lipid-rich plaque phenotype, is associated with enhanced plaque progression at 1-year follow-up. Where plaque progression occurred, low TAWSS was also observed. These findings suggest TSVI, in addition to low TAWSS, as a potential biomechanical predictor for plaque progression, showing promise for clinical translation to improve patient prognosis.</p