Scattering integral equation formulation for intravascular inclusion biosensing.

A dielectric waveguide, inserted into blood vessels, supports its basic mode that is being scattered by a near-field intravascular inclusion. A rigorous integral equation formulation is performed and the electromagnetic response from that inhomogeneity is semi-analytically evaluated. The detectability of the formation, based on spatial distribution of the recorded signal, is estimated by considering various inclusion sizes, locations and textural contrasts. The proposed technique, with its variants and generalizations, provides a generic versatile toolbox to efficiently model biosensor layouts involved in healthcare monitoring and disease screening.

Peripheral whole blood microRNA expression in relation to vascular function: a population-based study.

BACKGROUND: As key regulators of gene expression, microRNAs affect many cardiovascular mechanisms and have been associated with several cardiovascular diseases. In this study, we aimed to investigate the relation of whole blood microRNAs with several quantitative measurements of vascular function, and explore their biological role through an integrative microRNA-gene expression analysis. METHODS: Peripheral whole blood microRNA expression was assessed through RNA-Seq in 2606 participants (45.8% men, mean age: 53.93, age range: 30 to 95 years) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. Weighted gene co-expression network analysis was used to cluster microRNAs with highly correlated expression levels into 14 modules. Through linear regression models, we investigated the association between each module's expression and quantitative markers of vascular health, including pulse wave velocity, total arterial compliance index, cardiac index, stroke index, systemic vascular resistance index, reactive skin hyperemia and white matter hyperintensity burden. For each module associated with at least one trait, one or more hub-microRNAs driving the association were defined. Hub-microRNAs were further characterized through mapping to putative target genes followed by gene ontology pathway analysis. RESULTS: Four modules, represented by hub-microRNAs miR-320 family, miR-378 family, miR-3605-3p, miR-6747-3p, miR-6786-3p, and miR-330-5p, were associated with total arterial compliance index. Importantly, the miR-320 family module was also associated with white matter hyperintensity burden, an effect partially mediated through arterial compliance. Furthermore, hub-microRNA miR-192-5p was related to cardiac index. Functional analysis corroborated the relevance of the identified microRNAs for vascular function by revealing, among others, enrichment for pathways involved in blood vessel morphogenesis and development, angiogenesis, telomere organization and maintenance, and insulin secretion. CONCLUSIONS: We identified several microRNAs robustly associated with cardiovascular function, especially arterial compliance and cardiac output. Moreover, our results highlight miR-320 as a regulator of cerebrovascular damage, partly through modulation of vascular function. As many of these microRNAs were involved in biological processes related to vasculature development and aging, our results contribute to the understanding of vascular physiology and provide putative targets for cardiovascular disease prevention.

Overcoming big bottlenecks in vascular regeneration.

Bioengineering and regenerative medicine strategies are promising for the treatment of vascular diseases. However, current limitations inhibit the ability of these approaches to be translated to clinical practice. Here we summarize some of the big bottlenecks that inhibit vascular regeneration in the disease applications of aortic aneurysms, stroke, and peripheral artery disease. We also describe the bottlenecks preventing three-dimensional bioprinting of vascular networks for tissue engineering applications. Finally, we describe emerging technologies and opportunities to overcome these challenges to advance vascular regeneration.

Sensorless adaptive optics in the second near-infrared window for deep vascular imaging in vivo.

We have experimentally validated the use of sensorless adaptive optics (AO) to enhance laser scanning confocal microscopy in the second near-infrared (NIR II) spectral range, termed as AO-NIR II confocal microscopy. This approach harnesses a NIR II fluorophore, excited by an 808 nm wavelength and emitting beyond 1000 nm, to visualize intricate structures in deep brain tissues with the intact skull. By leveraging the reduced scattering and aberrations in the NIR II spectrum, we successfully captured a three-dimensional (3D) vascular structure map extending 310 µm beneath the skull. AO typically boosts the fluorescence signal by approximately 2-3 times, leading to a superior contrast and diminished smearing effects. Consequently, small blood vessels at various depths can be clearly visualized, which might otherwise remain undetectable without AO corrections.

Applications of extraembryonic tissue-derived cells in vascular tissue regeneration.

Vascular tissue engineering is a promising approach for regenerating damaged blood vessels and developing new therapeutic approaches for heart disease treatment. To date, different sources of cells have been recognized that offer assistance within the recovery of heart supply routes and veins with distinctive capacities and are compelling for heart regeneration. However, some challenges still remain that need to be overcome to establish the full potential application of these cells. In this paper, we review the different cell sources used for vascular tissue engineering, focusing on extraembryonic tissue-derived cells (ESCs), and elucidate their roles in cardiovascular disease. In addition, we highlight the intricate interplay between mechanical and biochemical factors in regulating mesenchymal stem cell (MSC) differentiation, offering insights into optimizing their application in vascular tissues.

Limited Nerve Regeneration across Acellular Nerve Allografts (ANAs) Coincides with Changes in Blood Vessel Morphology and the Development of a Pro-Inflammatory Microenvironment.

The use of acellular nerve allografts (ANAs) to reconstruct long nerve gaps (>3 cm) is associated with limited axon regeneration. To understand why ANA length might limit regeneration, we focused on identifying differences in the regenerative and vascular microenvironment that develop within ANAs based on their length. A rat sciatic nerve gap model was repaired with either short (2 cm) or long (4 cm) ANAs, and histomorphometry was used to measure myelinated axon regeneration and blood vessel morphology at various timepoints (2-, 4- and 8-weeks). Both groups demonstrated robust axonal regeneration within the proximal graft region, which continued across the mid-distal graft of short ANAs as time progressed. By 8 weeks, long ANAs had limited regeneration across the ANA and into the distal nerve (98 vs. 7583 axons in short ANAs). Interestingly, blood vessels within the mid-distal graft of long ANAs underwent morphological changes characteristic of an inflammatory pathology by 8 weeks post surgery. Gene expression analysis revealed an increased expression of pro-inflammatory cytokines within the mid-distal graft region of long vs. short ANAs, which coincided with pathological changes in blood vessels. Our data show evidence of limited axonal regeneration and the development of a pro-inflammatory environment within long ANAs.

Vascular smooth muscle cells exhibit elevated hypoxia-inducible Factor-1α expression in human blood vessel organoids, influencing osteogenic performance.

Considering the importance of alternative methodologies to animal experimentation, we propose an organoid-based biological model for in vitro blood vessel generation, achieved through co-culturing endothelial and vascular smooth muscle cells (VSMCs). Initially, the organoids underwent comprehensive characterization, revealing VSMCs (α-SMA + cells) at the periphery and endothelial cells (CD31+ cells) at the core. Additionally, ephrin B2 and ephrin B4, genes implicated in arterial and venous formation respectively, were used to validate the obtained organoid. Moreover, the data indicates exclusive HIF-1α expression in VSMCs, identified through various methodologies. Subsequently, we tested the hypothesis that the generated blood vessels have the capacity to modulate the osteogenic phenotype, demonstrating the ability of HIF-1α to promote osteogenic signals, primarily by influencing Runx2 expression. Overall, this study underscores that the methodology employed to create blood vessel organoids establishes an experimental framework capable of producing a 3D culture model of both venous and arterial endothelial tissues. This model effectively guides morphogenesis from mesenchymal stem cells through paracrine signaling, ultimately leading to an osteogenic acquisition phenotype, with the dynamic involvement of HIF-1α.

Entorhinal vessel density correlates with phosphorylated tau and TDP-43 pathology.

INTRODUCTION: The entorhinal cortex (EC) and perirhinal cortex (PC) are vulnerable to Alzheimer's disease. A triggering factor may be the interaction of vascular dysfunction and tau pathology. METHODS: We imaged post mortem human tissue at 100 µm3 with 7 T magnetic resonance imaging and manually labeled individual blood vessels (mean = 270 slices/case). Vessel density was quantified and compared per EC subfield, between EC and PC, and in relation to tau and TAR DNA-binding protein 43 (TDP-43) semiquantitative scores. RESULTS: PC was more vascularized than EC and vessel densities were higher in posterior EC subfields. Tau and TDP-43 strongly correlated with vasculature density and subregions with severe tau at the preclinical stage had significantly greater vessel density than those with low tau burden. DISCUSSION: These data impact cerebrovascular maps, quantification of subfield vasculature, and correlation of vasculature and pathology at early stages. The ordered association of vessel density, and tau or TDP-43 pathology, may be exploited in a predictive context. HIGHLIGHTS: Vessel density correlates with phosphorylated tau (p-tau) burden in entorhinal and perirhinal cortices. Perirhinal area 35 and posterior entorhinal cortex showed greatest p-tau burden but also the highest vessel density in the preclinical phase of Alzheimer's disease. We combined an ex vivo magnetic resonance imaging model and histopathology to demonstrate the 3D reconstruction of intracortical vessels and its spatial relationship to the pathology.

Dynamics of endothelial cells migration in nature-mimicking blood vessels.

Endothelial cells (ECs) migration is a crucial early step in vascular repair and tissue neovascularization. While extensive research has elucidated the biochemical drivers of endothelial motility, the impact of biophysical cues, including vessel geometry and topography, remains unclear. Herein, we present a novel approach to reconstruct 3D self-assembly blood vessels-on-a-chip that accurately replicates real vessel geometry and topography, surpassing conventional 2D flat tube formation models. This vessels-on-a-chip system enables real-time monitoring of vasculogenesis and ECs migration at high spatiotemporal resolution. Our findings reveal that ECs exhibit increased migration speed and directionality in response to narrower vessel geometries, transitioning from a rounded to a polarized morphology. These observations underscore the critical influence of vessel size in regulating ECs migration and morphology. Overall, our study highlights the importance of biophysical factors in shaping ECs behavior, emphasizing the need to consider such factors in future studies of endothelial function and vessel biology.

Deciphering Key microRNA Regulated Pathways in Tissue-Engineered Blood Vessels: Implications for Vascular Scaffold Production.

MicroRNAs (miRNAs) are non-coding RNAs involved in the regulation of gene expression associated with cell differentiation, proliferation, adhesion, and important biological functions such as inflammation. miRNAs play roles associated with the pathogenesis of chronic degenerative disorders including cardiovascular diseases. Understanding the influence of miRNAs and their target genes can effectively streamline the identification of key biologically active pathways that are important in the development of vascular grafts through the tissue engineering of blood vessels. To determine miRNA expression levels and identify miRNA target genes and pathways with biological roles in scaffolds that have been repopulated with adipose-derived stem cells (ASCs) generated through tissue engineering for the construction of blood vessels. miRNA quantification assays were performed in triplicate to determine miRNA expression in a total of 20 samples: five controls (natural inferior vena cava), five scaffolds recellularized with ASCs and differentiated into the endothelium (luminal layer), five samples of complete scaffolds seeded with ASCs differentiated into the endothelium (luminal layer) and smooth muscle (extraluminal layer), and five samples of ASC without cell differentiation. Several differentially expressed miRNAs were identified and predicted to modulate target genes with roles in key pathways associated with angiogenesis, vascular system control, and endothelial and smooth muscle regulation, including migration, proliferation, and growth. These findings underscore the involvement of these pathways in the regulatory mechanisms that are essential for vascular scaffold production through tissue engineering. Our research contributes to the knowledge of miRNA-regulated mechanisms, which may impact the design of vascular substitutes, and provide valuable insights for enhancing clinical practice. The molecular pathways regulated by miRNAs in tissue engineering of blood vessels (TEBV) allowed us to elucidate the main phenomena involved in cellular differentiation to constitute a blood vessel, with the main pathways being essential for angiogenesis, cellular differentiation, and differentiation into vascular smooth muscle.

Prediction of lymph node metastasis in T1 colorectal cancer based on combination of body composition and vascular invasion.

OBJECTIVES: Lymph node metastasis (LNM) in colorectal cancer (CRC) patients is not only associated with the tumor's local pathological characteristics but also with systemic factors. This study aims to assess the feasibility of using body composition and pathological features to predict LNM in early stage colorectal cancer (eCRC) patients. METHODS: A total of 192 patients with T1 CRC who underwent CT scans and surgical resection were retrospectively included in the study. The cross-sectional areas of skeletal muscle, subcutaneous fat, and visceral fat at the L3 vertebral body level in CT scans were measured using Image J software. Logistic regression analysis were conducted to identify the risk factors for LNM. The predictive accuracy and discriminative ability of the indicators were evaluated using receiver operating characteristic (ROC) curves. Delong test was applied to compare area under different ROC curves. RESULTS: LNM was observed in 32 out of 192 (16.7%) patients with eCRC. Multivariate analysis revealed that the ratio of skeletal muscle area to visceral fat area (SMA/VFA) (OR = 0.021, p = 0.007) and pathological indicators of vascular invasion (OR = 4.074, p = 0.020) were independent risk factors for LNM in eCRC patients. The AUROC for SMA/VFA was determined to be 0.740 (p < 0.001), while for vascular invasion, it was 0.641 (p = 0.012). Integrating both factors into a proposed predictive model resulted in an AUROC of 0.789 (p < 0.001), indicating a substantial improvement in predictive performance compared to relying on a single pathological indicator. CONCLUSION: The combination of the SMA/VFA ratio and vascular invasion provides better prediction of LNM in eCRC.

Analyzing solitary wave solutions of the nonlinear Murray equation for blood flow in vessels with non-uniform wall properties.

Solitary wave solutions are of great interest to bio-mathematicians and other scientists because they provide a basic description of nonlinear phenomena with many practical applications. They provide a strong foundation for the development of novel biological and medical models and therapies because of their remarkable behavior and persistence. They have the potential to improve our comprehension of intricate biological systems and help us create novel therapeutic approaches, which is something that researchers are actively investigating. In this study, solitary wave solutions of the nonlinear Murray equation will be discovered using a modified extended direct algebraic method. These solutions represent a uniform variation in blood vessel shape and diameter that can be used to stimulate blood flow in patients with cardiovascular disease. These solutions are newly in the literature, and give researchers an important tool for grasping complex biological systems. To see how the solitary wave solutions behave, graphs are displayed using Matlab.

Modeling and experimental study of the intervention forces between the guidewire and blood vessels.

A profound investigation of the interaction mechanics between blood vessels and guidewires is necessary to achieve safe intervention. An interactive force model between guidewires and blood vessels is established based on cardiovascular fluid dynamics theory and contact mechanics, considering two intervention phases (straight intervention and contact intervention at a corner named "J-vessel"). The contributing factors of the force model, including intervention conditions, guidewire characteristics, and intravascular environment, are analyzed. A series of experiments were performed to validate the availability of the interactive force model and explore the effects of influential factors on intervention force. The intervention force data were collected using a 2-DOF mechanical testing system instrumented with a force sensor. The guidewire diameter and material were found to significantly impact the intervention force. Additionally, the intervention force was influenced by factors such as blood viscosity, blood vessel wall thickness, blood flow velocity, as well as the interventional velocity and interventional mode. The experiment of the intervention in a coronary artery physical vascular model confirms the practicality validation of the predicted force model and can provide an optimized interventional strategy for vascular interventional surgery. The enhanced intervention strategy has resulted in a considerable reduction of approximately 21.97 % in the force exerted on blood vessels, effectively minimizing the potential for complications associated with the interventional surgery.

Nonlinear Elasticity of Blood Vessels and Vascular Grafts.

The transplantation of vascular grafts has emerged as a prevailing approach to address vascular disorders. However, the development of small-diameter vascular grafts is still in progress, as they serve in a more complicated mechanical environment than their counterparts with larger diameters. The biocompatibility and functional characteristics of small-diameter vascular grafts have been well developed; however, mismatch in mechanical properties between the vascular grafts and native arteries has not been accomplished, which might facilitate the long-term patency of small-diameter vascular grafts. From a point of view in mechanics, mimicking the nonlinear elastic mechanical behavior exhibited by natural blood vessels might be the state-of-the-art in designing vascular grafts. This review centers on elucidating the nonlinear elastic behavior of natural blood vessels and vascular grafts. The biological functionality and limitations associated with as-reported vascular grafts are meticulously reviewed and the future trajectory for fabricating biomimetic small-diameter grafts is discussed. This review might provide a different insight from the traditional design and fabrication of artificial vascular grafts.

Clinical, endoscopic and therapeutic features of bleeding Dieulafoy's lesions: case series and literature review.

OBJECTIVE: Dieulafoy's lesions (DLs) are a rare but potentially life-threatening source of gastrointestinal (GI) haemorrhage. They are responsible for roughly 1%-6.5% of all cases of acute non-variceal GI bleeding.Here, we describe retrospectively the clinical and endoscopic features, review the short-term and long-term outcomes of endoscopic management of bleeding DLs and we identify rate and risk factors, of recurrence and mortality in our endoscopic unit. DESIGN: Data were collected from patients presenting with GI haemorrhagic secondary to DLs between January 2018 and August 2023. Patients' medical records as well as endoscopic databases were retrospectively reviewed. Demographic data, risk factors, bleeding site, outcomes of endoscopy techniques, recurrence and mortality rate were taken into account. RESULTS: Among 1170 cases of GI bleeding, we identified only seven cases involving DLs. Median age was 74 years, with a male-to-female ratio of 2.5. 75% of patients had significant comorbidities, mainly cardiovascular diseases. Only anticoagulant and antiplatelet agents were significantly associated with DLs. All patients were presented with GI bleeding as their initial symptom. The initial endoscopy led to a diagnosis in 85% of the cases. Initial haemostasis was obtained in all patients treated endoscopically. Nevertheless, the study revealed early recurrence in two out of three patients treated solely with epinephrine injection or argon plasma coagulation. In contrast, one of three patients who received combined therapy, experienced late recurrence (average follow-up of 1 year). Pathological diagnosis was necessary in one case. One patient (14%) died of haemorrhagic shock. Average length of hospital stay was 3 days. CONCLUSION: Although rare, DLs may be responsible for active, recurrent and unexplained GI bleeding. Thanks to the emergence of endoscopic therapies, the recurrence rate has decreased and the prognosis has highly improved. Therefore, the endoscopic approach remains the first choice to manage bleeding DLs.

Development of an Automated Morphometric Approach to Assess Vascular Outcomes following Exposure to Environmental Chemicals in Zebrafish.

BACKGROUND: Disruptions in vascular formation attributable to chemical insults is a pivotal risk factor or potential etiology of developmental defects and various disease settings. Among the thousands of chemicals threatening human health, the highly concerning groups prevalent in the environment and detected in biological monitoring in the general population ought to be prioritized because of their high exposure risks. However, the impacts of a large number of environmental chemicals on vasculature are far from understood. The angioarchitecture complexity and technical limitations make it challenging to analyze the entire vasculature efficiently and identify subtle changes through a high-throughput in vivo assay. OBJECTIVES: We aimed to develop an automated morphometric approach for the vascular profile and assess the vascular morphology of health-concerning environmental chemicals. METHODS: High-resolution images of the entire vasculature in Tg(fli1a:eGFP) zebrafish were collected using a high-content imaging platform. We established a deep learning-based quantitative framework, ECA-ResXUnet, combined with MATLAB to segment the vascular networks and extract features. Vessel scores based on the rates of morphological changes were calculated to rank vascular toxicity. Potential biomarkers were identified by vessel-endothelium-gene-disease integrative analysis. RESULTS: Whole-trunk blood vessels and the cerebral vasculature in larvae exposed to 150 representative chemicals were automatically segmented as comparable to human-level accuracy, with sensitivity and specificity of 95.56% and 95.81%, respectively. Chemical treatments led to heterogeneous vascular patterns manifested by 31 architecture indexes, and the common cardinal vein (CCV) was the most affected vessel. The antipsychotic medicine haloperidol, flame retardant 2,2-bis(chloromethyl)trimethylenebis[bis(2-chloroethyl) phosphate], and tert-butylphenyl diphenyl phosphate ranked as the top three in vessel scores. Pesticides accounted for the largest group, with a vessel score of ≥1, characterized by a remarkable inhibition of subintestinal venous plexus and delayed development of CCV. Multiple-concentration evaluation of nine per- and polyfluoroalkyl substances (PFAS) indicated a low-concentration effect on vascular impairment and a positive association between carbon chain length and benchmark concentration. Target vessel-directed single-cell RNA sequencing of fli1a+ cells from larvae treated with λ-cyhalothrin, perfluorohexanesulfonic acid, or benzylbutyl phthalate, along with vessel-endothelium-gene-disease integrative analysis, uncovered potential associations with vascular disorders and identified biomarker candidates. DISCUSSION: This study provides a novel paradigm for phenotype-driven screenings of vascular-disrupting chemicals by converging morphological and transcriptomic profiles at a high-resolution level, serving as a powerful tool for large-scale toxicity tests. Our approach and the high-quality morphometric data facilitate the precise evaluation of vascular effects caused by environmental chemicals. https://doi.org/10.1289/EHP13214.

Simulation of stress in a blood vessel due to plaque sediments in coronary artery disease.

Atherosclerosis is a cardiovascular disease mainly caused by plaque deposition in blood vessels. Plaque comprises components such as thrombosis, fibrin, collagen, and lipid core. It plays an essential role in inducing rupture in a blood vessel. Generally, Plaque could be described as three kinds of elastic models: cellular Plaque, hypocellular Plaque, and calcified Plaque. The present study aimed to investigate the behavior of atherosclerotic plaque rupture according to different lipid cores using Fluid-Structure Interaction (FSI). The blood vessel was also varied with different thicknesses (0.05, 0.25, and 0.5 mm). In this study, FSI simulation with a cellular plaque model with various thicknesses was investigated to obtain information on plaque rupture. Results revealed that the blood vessel with Plaque having a lipid core represents higher stresses than those without a lipid core. Blood vessels' thin thickness, like a thin cap, results in more considerable than Von Mises stress. The result also suggests that even at low fracture stress, the risk of rupture due to platelet decomposition at the gap was more significant for cellular plaques.

Vascular development, remodeling and maturation.

The development of the vascular system is crucial in supporting the growth and health of all other organs in the body, and vascular system dysfunction is the major cause of human morbidity and mortality. This chapter discusses three successive processes that govern vascular system development, starting with the differentiation of the primitive vascular system in early embryonic development, followed by its remodeling into a functional circulatory system composed of arteries and veins, and its final maturation and acquisition of an organ specific semi-permeable barrier that controls nutrient uptake into tissues and hence controls organ physiology. Along these steps, endothelial cells forming the inner lining of all blood vessels acquire extensive heterogeneity in terms of gene expression patterns and function, that we are only beginning to understand. These advances contribute to overall knowledge of vascular biology and are predicted to unlock the unprecedented therapeutic potential of the endothelium as an avenue for treatment of diseases associated with dysfunctional vasculature.

Leptin signaling promotes blood vessel formation in the Xenopus tail during the embryo-larval transition.

The signals that regulate peripheral blood vessel formation during development are still under investigation. The hormone leptin promotes blood vessel formation, adipose tissue establishment and expansion, tumor growth, and wound healing, but the underlying mechanisms for these actions are currently unknown. We investigated whether leptin promotes angiogenesis in the developing tail fin using embryonic transgenic xflk-1:GFP Xenopus laevis, which express a green fluorescent protein on vascular endothelial cells to mark blood vessels. We found that leptin protein is expressed in endothelial cells of developing blood vessels and that leptin treatment via injection increased phosphorylated STAT3 signaling, which is indicative of leptin activation of its receptor, in blood vessels of the larval tail fin. Leptin administration via media increased vessel length, branching, and reconnection with the cardinal vein, while decreased leptin signaling via immunoneutralization had an opposing effect on vessel development. We also observed disorganization of major vessels and microvessels of the tail fin and muscle when leptin signaling was decreased. Reduced leptin signaling lowered mRNA expression of cenpk, gpx1, and mmp9, markers for cell proliferation, antioxidation, and extracellular matrix remodeling/cell migration, respectively, in the developing tail, providing insight into three possible mechanisms underlying leptin's promotion of angiogenesis. Together these results illustrate that leptin levels are correlated with embryonic angiogenesis and that leptin coordinates multiple aspects of blood vessel growth and development, showing that leptin is an important morphogen during embryonic development.