Does low and oscillatory wall shear stress correlate spatially with early atherosclerosis? A systematic review

Low and oscillatory wall shear stress is widely assumed to play a key role in the initiation and development of atherosclerosis. Indeed, some studies have relied on the low shear theory when developing diagnostic and treatment strategies for cardiovascular disease. We wished to ascertain if this consensus is justified by published data. We performed a systematic review of papers that compare the localization of atherosclerotic lesions with the distribution of haemodynamic indicators calculated using computational fluid dynamics. The review showed that although many articles claim their results conform to the theory, it has been interpreted in different ways: a range of metrics has been used to characterize the distribution of disease, and they have been compared with a range of haemodynamic factors. Several studies, including all of those making systematic point-by-point comparisons of shear and disease, failed to find the expected relation. The various pre- and post-processing techniques used by different groups have reduced the range of shears over which correlations were sought, and in some cases are mutually incompatible. Finally, only a subset of the known patterns of disease has been investigated. The evidence for the low/oscillatory shear theory is less robust than commonly assumed. Longitudinal studies starting from the healthy state, or the collection of average flow metrics derived from large numbers of healthy vessels, both in conjunction with point-by-point comparisons using appropriate statistical techniques, will be necessary to improve our understanding of the relation between blood flow and atherogenesis

The Effects of Time Varying Curvature on Species Transport in Coronary Arteries

Alterations in mass transport patterns of low-density lipoproteins (LDL) and oxygen are known to cause atherosclerosis in larger arteries. We hypothesise that the species transport processes in coronary arteries may be affected by their physiological motion, a factor which has not been considered widely in mass transfer studies. Hence, we numerically simulated the mass transport of LDL and oxygen in an idealized moving coronary artery model under both steady and pulsatile flow conditions. A physiological inlet velocity and a sinusoidal curvature waveform were specified as velocity and wall motion boundary conditions. The results predicted elevation of LDL flux, impaired oxygen flux and low wall shear stress (WSS) along the inner wall of curvature, a predilection site for atherosclerosis. The wall motion induced changes in the velocity and WSS patterns were only secondary to the pulsatile flow effects. The temporal variations in flow and WSS due to the flow pulsation and wall motion did not affect temporal changes in the species wall flux. However, the wall motion did alter the time-averaged oxygen and LDL flux in the order of 26% and 12% respectively. Taken together, these results suggest that the wall motion may play an important role in coronary arterial transport processes and emphasise the need for further investigation

Distribution of Cortical Endoplasmic Reticulum Determines Positioning of Endocytic Events in Yeast Plasma Membrane

In many eukaryotes, a significant part of the plasma membrane is closely associated with the dynamic meshwork of cortical endoplasmic reticulum (cortical ER). We mapped temporal variations in the local coverage of the yeast plasma membrane with cortical ER pattern and identified micron-sized plasma membrane domains clearly different in cortical ER persistence. We show that clathrin-mediated endocytosis is initiated outside the cortical ER-covered plasma membrane zones. These cortical ER-covered zones are highly dynamic but do not overlap with the immobile and also endocytosis-inactive membrane compartment of Can1 (MCC) and the subjacent eisosomes. The eisosomal component Pil1 is shown to regulate the distribution of cortical ER and thus the accessibility of the plasma membrane for endocytosis

ER sliding dynamics and ER–mitochondrial contacts occur on acetylated microtubules

Movement of the ER and mitochondria is coupled by limited interactions of the ER with a subset of posttranslationally modified microtubules

Toward visualization of nanomachines in their native cellular environment

The cellular nanocosm is made up of numerous types of macromolecular complexes or biological nanomachines. These form functional modules that are organized into complex subcellular networks. Information on the ultra-structure of these nanomachines has mainly been obtained by analyzing isolated structures, using imaging techniques such as X-ray crystallography, NMR, or single particle electron microscopy (EM). Yet there is a strong need to image biological complexes in a native state and within a cellular environment, in order to gain a better understanding of their functions. Emerging methods in EM are now making this goal reachable. Cryo-electron tomography bypasses the need for conventional fixatives, dehydration and stains, so that a close-to-native environment is retained. As this technique is approaching macromolecular resolution, it is possible to create maps of individual macromolecular complexes. X-ray and NMR data can be ‘docked’ or fitted into the lower resolution particle density maps to create a macromolecular atlas of the cell under normal and pathological conditions. The majority of cells, however, are too thick to be imaged in an intact state and therefore methods such as ‘high pressure freezing’ with ‘freeze-substitution followed by room temperature plastic sectioning’ or ‘cryo-sectioning of unperturbed vitreous fully hydrated samples’ have been introduced for electron tomography. Here, we review methodological considerations for visualizing nanomachines in a close-to-physiological, cellular context. EM is in a renaissance, and further innovations and training in this field should be fully supported

Axial stent strut angle influences wall shear stress after stent implantation: analysis using 3D computational fluid dynamics models of stent foreshortening

INTRODUCTION: The success of vascular stents in the restoration of blood flow is limited by restenosis. Recent data generated from computational fluid dynamics (CFD) models suggest that the vascular geometry created by an implanted stent causes local alterations in wall shear stress (WSS) that are associated with neointimal hyperplasia (NH). Foreshortening is a potential limitation of stent design that may affect stent performance and the rate of restenosis. The angle created between axially aligned stent struts and the principal direction of blood flow varies with the degree to which the stent foreshortens after implantation. METHODS: In the current investigation, we tested the hypothesis that stent foreshortening adversely influences the distribution of WSS and WSS gradients using time-dependent 3D CFD simulations of normal arteries based on canine coronary artery measurements of diameter and blood flow. WSS and WSS gradients were calculated using conventional techniques in ideal (16 mm) and progressively foreshortened (14 and 12 mm) stented computational vessels. RESULTS: Stent foreshortening increased the intrastrut area of the luminal surface exposed to low WSS and elevated spatial WSS gradients. Progressive degrees of stent foreshortening were also associated with strut misalignment relative to the direction of blood flow as indicated by analysis of near-wall velocity vectors. CONCLUSION: The current results suggest that foreshortening may predispose the stented vessel to a higher risk of neointimal hyperplasia

Author Correction: SciPy 1.0: fundamental algorithms for scientific computing in Python.

An amendment to this paper has been published and can be accessed via a link at the top of the paper