The relationship between wall shear stress distributions and intimal thickening in the human abdominal aorta

Purpose

The goal of this work was to determine wall shear stress (WSS) patterns in the human abdominal aorta and to compare these patterns to measurements of intimal thickness (IT) from autopsy samples.

Methods

The WSS was experimentally measured using the laser photochromic dye tracer technique in an anatomically faithful in vitro model based on CT scans of the abdominal aorta in a healthy 35-year-old subject. IT was quantified as a function of circumferential and axial position using light microscopy in ten human autopsy specimens.

Results

The histomorphometric analysis suggests that IT increases with age and that the distribution of intimal thickening changes with age. The lowest WSS in the flow model was found on the posterior wall inferior to the inferior mesenteric artery, and coincided with the region of most prominent IT in the autopsy samples. Local geometrical features in the flow model, such as the expansion at the inferior mesenteric artery (common in younger individuals), strongly influenced WSS patterns. The WSS was found to correlate negatively with IT (r² = 0.3099; P = 0.0047).

Conclusion

Low WSS in the abdominal aorta is co-localized with IT and may be related to atherogenesis. Also, rates of IT in the abdominal aorta are possibly influenced by age-related geometrical changes.

     

Relationship between plaque composition by virtual histology intravascular ultrasound and clinical outcomes after percutaneous coronary intervention in saphenous vein graft disease patients: study protocol of a prospective cohort study

Background

Plaque composition and morphologic characteristics identified by virtual histology intravascular ultrasound (VH-IVUS) can determine plaques at increased risk of clinical events following percutaneous coronary intervention (PCI) among coronary artery disease (CAD) patients. However, there have been few studies to investigate the relationship between plaque composition of saphenous vein graft (SVG) by VH-IVUS and clinical outcomes in patients with saphenous vein graft disease (SVGD) undergoing PCI. The purpose of this study is to determine whether plaque components and characteristics by VH-IVUS can predict major adverse cardiac events (MACEs) among SVGD patients undergoing PCI.

Methods/design

This is a prospective cohort study conducted in Tianjin Chest Hospital, China. Participants with SVGD referred for PCI will be invited to participate in this study, and will be followed up at 1, 6, 12, 24 and 36?months post-PCI to assess clinical outcomes.The planned sample size is 175 subjects. We will recruit subjects with SVGD scheduled to receive PCI, aged 18–80?years, with a history of previous coronary artery bypass graft (CABG) surgery more than 1?year ago, and willing to participate in the study and sign informed consent.The composite primary study endpoint is the incidence of MACEs after PCI for SVGD, including death from cardiac causes, non-fatal myocardial infarction, unplanned target lesion revascularization (TLR) and target vessel revascularization (TVR). The primary outcome analysis will be presented as Kaplan-Meier estimates and the primary outcome analysis will be carried out using a Cox proportional hazards regression model.

Discussion

Once the predictive values of plaque components and characteristics by VH-IVUS on subsequent clinical outcomes are determined among SVGD patients undergoing PCI, an innovative prediction tool of clinical outcomes for SVGD patients undergoing PCI will be created, which may lead to the development of new methods of risk stratification and intervention guidance.

Trial registration

The study is registered to ClinicalTrials.gov (NCT03175952).

     

Artery buckling affects the mechanical stress in atherosclerotic plaques

Background

Tortuous arteries are often seen in patients with hypertension and atherosclerosis. While the mechanical stress in atherosclerotic plaque under lumen pressure has been studied extensively, the mechanical stability of atherosclerotic arteries and subsequent effect on the plaque stress remain unknown. To this end, we investigated the buckling and post-buckling behavior of model stenotic coronary arteries with symmetric and asymmetric plaque.

Methods

Buckling analysis for a model coronary artery with symmetric and asymmetric plaque was conducted using finite element analysis based on the dimensions and nonlinear anisotropic materials properties reported in the literature.

Results

Artery with asymmetric plaque had lower critical buckling pressure compared to the artery with symmetric plaque and control artery. Buckling increased the peak stress in the plaque and led to the development of a high stress concentration in artery with asymmetric plaque. Stiffer calcified tissue and severe stenosis increased the critical buckling pressure of the artery with asymmetric plaque.

Conclusions

Arteries with atherosclerotic plaques are prone to mechanical buckling which leads to a high stress concentration in the plaques that can possibly make the plaques prone to rupture.

     

Correlation between quantitative analysis of wall shear stress and intima-media thickness in atherosclerosis development in carotid arteries

Background

This paper presents quantitative analysis of blood flow shear stress by measuring the carotid arterial wall shear stress (WSS) and the intima-media thickness (IMT) of experimental rabbits fed with high-fat feedstuff on a weekly basis in order to cause atherosclerosis.

Methods

This study is based on establishing an atherosclerosis model of high-fat rabbits, and measuring the rabbits’ common carotid arterial WSS of the experimental group and control group on a weekly basis. Detailed analysis was performed by using WSS quantification.

Results

We have demonstrated small significant difference of rabbit carotid artery WSS between the experimental group and the control group (P<0.01) from the 1st week onwards, while the IMT of experimental group had larger differences from 5th week compared with the control group (P<0.05). Next, we have shown that with increasing blood lipids, the rabbit carotid artery shear stress decreases and the rabbit carotid artery IMT goes up. The decrease of shear stress appears before the start of IMT growth. Furthermore, our receiver operator characteristic (ROC) curve analysis showed that when the mean value of shear stress is 1.198 dyne/cm², the rabbit common carotid atherosclerosis fatty streaks sensitivity is 89.8%, and the specificity is 81.3%. The area under the ROC curve is 0.9283.

Conclusions

All these data goes to show that WSS decreasing to 1.198 dyne/cm² can be used as an indicator that rabbit common carotid artery comes into the period of fibrous plaques. In conclusion, our study is able to find and confirm that the decrease of the arterial WSS can predict the occurrence of atherosclerosis earlier, and offer help for positive clinical intervention.

     

Numerical simulation on the effects of drug eluting stents at different Reynolds numbers on hemodynamic and drug concentration distribution

Background

The changes of hemodynamics and drug concentration distribution caused by the implantation of drug eluting stents (DESs) in curved vessels have significant effects on In-Stent Restenosis.

Methods

A 3D virtual stent with 90°curvature was modelled and the distribution of wall shear stress (WSS) and drug concentration in this model were numerically studied at Reynolds numbers of 200, 400, 600, 800.

Results

The results showed that (1) the intensity of secondary flow at the 45° cross-section was stronger than that at the 90° cross-section; (2) As the Reynolds number increases, the WSS decreases. When the Reynolds number reaches 600, the low-WSS region only accounts for 3% of the total area. (3) The effects of Reynolds number on drug concentration in the vascular wall decreases in proportionally and then the blood velocity increased 4 times, the drug concentration in the vascular wall decreased by about 30%. (4) The size of the high drug concentration region is inversely proportional to the Reynolds number. As the blood velocity increases, the drug concentration in the DES decreases, especially at the outer bend.

Conclusions

It is beneficial for the patient to decrease vigorous activities and keep calm at the beginning of the stent implantation, because a substantial amount of the drug is released in the first two months of stent implantation, thus a calm status is conducive to drug release and absorption; Subsequently, appropriate exercise which increases the blood velocity is helpful in decreasing regions of low-WSS.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

Finite element analysis of mechanics of neovessels with intraplaque hemorrhage in carotid atherosclerosis

Background

Intraplaque hemorrhage is a widely known factor facilitating plaque instability. Neovascularization of plaque can be regarded as a compensatory response to the blood supply in the deep intimal and medial areas of the artery. Due to the physiological function, the deformation of carotid atherosclerotic plaque would happen under the action of blood pressure and blood flow. Neovessels are subject to mechanical loading and likely undergo deformation. The rupture of neovessels may deteriorate the instability of plaque. This study focuses on the local mechanical environments around neovessels and investigates the relationship between the biomechanics and the morphological specificity of neovessels.

Methods

Stress and stretch were used to evaluate the rupture risk of the neovessels in plaque. Computational structural analysis was performed based on two human carotid plaque slice samples. Two-dimensional models containing neovessels and other components were built according to the plaque slice samples. Each component was assumed to be non-linear isotropic, piecewise homogeneous and incompressible. Different mechanical boundary conditions, i.e. static pressures, were imposed in the carotid lumen and neovessels lumen respectively. Finite element method was used to simulate the mechanical conditions in the atherosclerotic plaque.

Results

Those neovessels closer to the carotid lumen undergo larger stress and stretch. With the same distance to the carotid lumen, the longer the perimeter of neovessels is, the larger stress and the deformation of the neovessels will be. Under the same conditions, the neovessels with larger curvature suffer greater stress and stretch. Neovessels surrounded by red blood cells undergo a much larger stretch.

Conclusions

Local mechanical conditions may result in the hemorrhage of neovessels and accelerate the rupture of plaque. The mechanical environments of the neovessel are related to its shape, curvature, distance to the carotid lumen and the material properties of plaque.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.

     

KniMet: a pipeline for the processing of chromatography–mass spectrometry metabolomics data

Introduction

Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.

Objectives

Merge in the same platform the steps required for metabolomics data processing.

Methods

KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.

Results

The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.

Conclusion

KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.

     

A methodology for elucidating regulatory mechanisms leading to changes in lipid profiles

Introduction

It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.

Objectives

This work simplifies this process.

Methods

A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.

Results

The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.

Conclusion

This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

Metabolites predict cardiovascular disease events in persons living with HIV: a pilot case–control study

Introduction

Persons living with HIV (PLWH) are at higher risk for cardiovascular disease (CVD) events than uninfected persons. Current risk-stratification methods to define PLWH at highest risk for CVD events are lacking.

Methods

Using tandem flow injection mass spectrometry, we quantified plasma levels of 60 metabolites in 24 matched pairs of PLWH [1:1 with and without known coronary artery disease (CAD)]. Metabolite levels were reduced to interpretable factors using principal components analysis.

Results

Factors derived from short-chain dicarboxylacylcarnitines (SCDA) (p?=?0.08) and glutamine/valine (p?=?0.003) were elevated in CAD cases compared to controls.

Conclusion

SCDAs and glutamine/valine may be valuable markers of cardiovascular risk among persons living with HIV in the future, pending validation in larger cohorts.

     

Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results

Background

Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue.

Methods

Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue.

Results

Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen.

Conclusions

Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large discrepancies, future studies should seek to employ vessel-appropriate material models to simulate the response of diseased femoral tissue in order to obtain the most accurate numerical results.

     

Metabolomic profiling of maternal hair suggests rapid development of intrahepatic cholestasis of pregnancy

Introduction

Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.

Objective

Investigate the maternal hair metabolome for predictive biomarkers of ICP.

Methods

The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.

Results

Of 105 metabolites detected in hair, none were significantly associated with ICP.

Conclusion

Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.

     

Quantitative analysis of tetrahydrofolate metabolites from <Emphasis Type="Italic">clostridium autoethanogenum</Emphasis>

Introduction

Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.

Objective

To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.

Methods

Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.

Results

Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.

Conclusion

Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.

     

Extraction of natural products from bark of <Emphasis Type="Italic">Betula pendula</Emphasis> using ionic liquids

Introduction

Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.

Objectives

To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.

Methods

The extracted compounds were analyzed by LC/MS and GC/MS.

Results

The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.

Conclusion

From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.

     

The dental calculus metabolome in modern and historic samples

Introduction

Dental calculus is a mineralized microbial dental plaque biofilm that forms throughout life by precipitation of salivary calcium salts. Successive cycles of dental plaque growth and calcification make it an unusually well-preserved, long-term record of host-microbial interaction in the archaeological record. Recent studies have confirmed the survival of authentic ancient DNA and proteins within historic and prehistoric dental calculus, making it a promising substrate for investigating oral microbiome evolution via direct measurement and comparison of modern and ancient specimens.

Objective

We present the first comprehensive characterization of the human dental calculus metabolome using a multi-platform approach.

Methods

Ultra performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS) quantified 285 metabolites in modern and historic (200 years old) dental calculus, including metabolites of drug and dietary origin. A subset of historic samples was additionally analyzed by high-resolution gas chromatography–MS (GC–MS) and UPLC–MS/MS for further characterization of metabolites and lipids. Metabolite profiles of modern and historic calculus were compared to identify patterns of persistence and loss.

Results

Dipeptides, free amino acids, free nucleotides, and carbohydrates substantially decrease in abundance and ubiquity in archaeological samples, with some exceptions. Lipids generally persist, and saturated and mono-unsaturated medium and long chain fatty acids appear to be well-preserved, while metabolic derivatives related to oxidation and chemical degradation are found at higher levels in archaeological dental calculus than fresh samples.

Conclusions

The results of this study indicate that certain metabolite classes have higher potential for recovery over long time scales and may serve as appropriate targets for oral microbiome evolutionary studies.

     

Vasospasm is a significant factor in cyclosporine-induced neurotoxicity: Case report

Background

The aetiology of central nervous system lesions observed in cerebral cyclosporine neurotoxicity remains controversial.

Case presentation

We report a 48-year-old woman with a non-severe aplastic anaemia who presented with stroke-like episodes while on cyclosporine treatment.Transcranial Doppler ultrasound revealed severely elevated flow velocities in several cerebral vessels, consistent with vasospasm. Immediately after reducing the cyclosporine dose, the stroke-like episodes disappeared. Only after cyclosporine withdrawal the transcranial Doppler ultrasound abnormalities fully resolved.

Conclusions

This case demonstrates a significant role of vasospasm in the pathway of cyclosporine-induced neurotoxicity. Transcranial Doppler ultrasound is an effective tool for the diagnosis and follow-up of cyclosporine-induced vasospasm.

     

<Emphasis Type="Italic">massPix</Emphasis>: an R package for annotation and interpretation of mass spectrometry imaging data for lipidomics

Introduction

Mass spectrometry imaging (MSI) experiments result in complex multi-dimensional datasets, which require specialist data analysis tools.

Objectives

We have developed massPix—an R package for analysing and interpreting data from MSI of lipids in tissue.

Methods

massPix produces single ion images, performs multivariate statistics and provides putative lipid annotations based on accurate mass matching against generated lipid libraries.

Results

Classification of tissue regions with high spectral similarly can be carried out by principal components analysis (PCA) or k-means clustering.

Conclusion

massPix is an open-source tool for the analysis and statistical interpretation of MSI data, and is particularly useful for lipidomics applications.