Human Vein Research Articles

The role of peripheral venous distension reflex in regulating hemodynamics: mini review

Significant volume is pooled in veins in humans and the amount is dramatically altered by various physiological stresses and diseases. Several animal and human studies demonstrated that limb venous distension evoked significant increases in blood pressure and sympathetic nerve activity (venous distension reflex, VDR). VDR has attracted much attention because of its potential to explain the still unknown mechanism of autonomic dysfunction in several diseases, which would lead to a new treatment approach. This mini review discusses accumulated evidence of VDR at this point and what should be investigated in the future to apply the current understanding of VDR in clinical practice.

Novel Strategy for Human Deep Vein Thrombosis Diagnosis Based on Metabolomics and Stacking Machine Learning.

Deep vein thrombosis (DVT) is a serious health issue that often leads to considerable morbidity and mortality. Diagnosis of DVT in a clinical setting, however, presents considerable challenges. The fusion of metabolomics techniques and machine learning methods has led to high diagnostic and prognostic accuracy for various pathological conditions. This study explored the synergistic potential of dual-platform metabolomics (specifically, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS)) to expand the detection of metabolites and improve the precision of DVT diagnosis. Sixty-one differential metabolites were identified in serum from DVT patients: 22 from GC-MS and 39 from LC-MS. Among these, five key metabolites were highlighted by SHapley Additive exPlanations (SHAP)-guided feature engineering and then used to develop a stacking diagnostic model. Additionally, a user-friendly interface application system was developed to streamline and automate the application of the diagnostic model, enhancing its practicality and accessibility for clinical use. This work showed that the integration of dual-platform metabolomics with a stacking machine learning model enables faster and more accurate diagnosis of DVT in clinical environments.

Generation of a human induced pluripotent stem cell (iPSC, DVSi001-A) with a heterozygous mutation in KRAS (A209T)

Human varicose veins are commonly claimed to be responsible for lower limb symptoms. Mutation in KRAS gene has been implicated in various diseases, including cancers and vascular diseases. While little known about the novel mutation in KRAS gene and its contribution to the development of varicose veins. Here, we have generated human induced pluripotent stem cell (iPSC) line, which harboured a novel mutation in KRAS (c.209A>T) gene. This cell line provided a novel tool for understanding the mechanism of KRAS mutation in the pathogenesis of varicose veins.

Microarray analysis demonstrates up-regulation of the endothelin-1 gene with compensatory down-regulation of the ETA receptor gene in human portal vein.

High blood pressure in the portal vein, portal hypertension (PH), is the final common pathway in liver cirrhosis regardless of aetiology. Complications from PH are the major cause of morbidity and mortality in these patients. Current drug therapy to reduce portal pressure is mainly limited to β-adrenergic receptor blockade but approximately 40% of patients do not respond. Our aim was to use microarray to measure the expression of ∼20,800 genes in portal vein from patients with PH undergoing transplantation for liver cirrhosis (PH, n=12) versus healthy vessels (control, n=9) to identify potential drug targets to improve therapy. Expression of 9,964 genes above background was detected in portal vein samples. Comparing PH veins versus control (adjusted P-value < 0.05, fold change > 1.5) identified 548 up-regulated genes and 1,996 down-regulated genes. The 2,544 differentially expressed genes were subjected to pathway analysis. We identified 49 significantly enriched pathways. The endothelin pathway was ranked the tenth most significant, the only vasoconstrictive pathway to be identified. ET-1 gene (EDN1) was significantly up-regulated, consistent with elevated levels of ET-1 peptide previously measured in PH and cirrhosis. ETA receptor gene (EDNRA) was significantly down-regulated, consistent with an adaptive response to increased peptide levels in the portal vein but there was no change in the ETB gene (EDNRB). The results provide further support for evaluating the efficacy of ETA receptor antagonists as a potential therapy in addition to β-blockers in patients with PH and cirrhosis.

Expression of fibroblast activation protein-α in human deep vein thrombosis

BackgroundFibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is associated with wound healing, cancer-associated fibroblasts, and chronic fibrosing diseases. However, its expression in deep vein thrombosis (DVT) remains unclear. Therefore, this study investigated FAP expression and localization in DVT. MethodsWe performed pathological analyses of the aspirated thrombi of patients with DVT (n = 14), classifying thrombotic areas in terms of fresh, cellular lysis, and organizing reaction components. The organizing reaction included endothelialization and fibroblastic reaction. We immunohistochemically examined FAP-expressed areas and cells, and finally analyzed FAP expression in cultured dermal fibroblasts. ResultsAll the aspirated thrombi showed a heterogeneous mixture of at least two of the three thrombotic areas. Specifically, 83 % of aspirated thrombi showed fresh and organizing reaction components. Immunohistochemical expression of FAP was restricted to the organizing area. Double immunofluorescence staining showed that FAP in the thrombi was mainly expressed in vimentin-positive or α-smooth muscle actin-positive fibroblasts. Some CD163-positive macrophages expressed FAP. FAP mRNA and protein levels were higher in fibroblasts with low-proliferative activity cultured under 0.1 % fetal bovine serum (FBS) than that under 10 % FBS. Fibroblasts cultured in 10 % FBS showed a significant decrease in FAP mRNA levels following supplementation with hemin, but not with thrombin. ConclusionsThe heterogeneous composition of venous thrombi suggests a multistep thrombus formation process in human DVT. Further, fibroblasts or myofibroblasts may express FAP during the organizing process. FAP expression may be higher in fibroblasts with low proliferative activity.

Myocardin related transcription factor and galectin-3 drive lipid accumulation in human blood vessels

ObjectiveDiabetes and hypertension are important risk factors for vascular disease, including atherosclerosis. A driving factor in this process is lipid accumulation in smooth muscle cells of the vascular wall. The glucose- and mechano-sensitive transcriptional coactivator, myocardin-related transcription factor A (MRTF-A/MKL1) can promote lipid accumulation in cultured human smooth muscle cells and contribute to the formation of smooth muscle-derived foam cells. The purpose of this study was to determine if intact human blood vessels ex vivo can be used to evaluate lipid accumulation in the vascular wall, and if this process is dependent on MRTF and/or galectin-3/LGALS3. Galectin-3 is an early marker of smooth muscle transdifferentiation and a potential mediator for foam cell formation and atherosclerosis. Approach and resultsHuman mammary arteries and saphenous veins were exposed to altered cholesterol and glucose levels in an organ culture model. Accumulation of lipids, quantified by Oil Red O, was increased by cholesterol loading and elevated glucose concentrations. Pharmacological inhibition of MRTF with CCG-203971 decreased lipid accumulation, whereas adenoviral-mediated overexpression of MRTF-A had the opposite effect. Cholesterol-induced expression of galectin-3 was decreased after inhibition of MRTF. Importantly, pharmacological inhibition of galectin-3 with GB1107 reduced lipid accumulation in the vascular wall after cholesterol loading. ConclusionEx vivo organ culture of human arteries and veins can be used to evaluate lipid accumulation in the intact vascular wall, as well as adenoviral transduction and pharmacological inhibition. Although MRTF and galectin-3 may have beneficial, anti-inflammatory effects under certain circumstances, our results, which demonstrate a significant decrease in lipid accumulation, support further evaluation of MRTF- and galectin-3-inhibitors for therapeutic intervention against atherosclerotic vascular disease.

Inflammatory risk contributes to post-COVID endothelial dysfunction through anti-ACKR1 autoantibody.

Subclinical vascular impairment can be exacerbated in individuals who experience sustained inflammation after COVID-19 infection. Our study explores the prevalence and impact of autoantibodies on vascular dysfunction in healthy COVID-19 survivors, an area that remains inadequately investigated. Focusing on autoantibodies against the atypical chemokine receptor 1 (ACKR1), COVID-19 survivors demonstrated significantly elevated anti-ACKR1 autoantibodies, correlating with systemic cytokines, circulating damaged endothelial cells, and endothelial dysfunction. An independent cohort linked these autoantibodies to increased vascular disease outcomes during a median 6.7-yr follow-up. We analyzed a single-cell transcriptome atlas of endothelial cells from diverse mouse tissues, identifying enriched Ackr1 expressions in venous regions of the brain and soleus muscle vasculatures, which holds intriguing implications for tissue-specific venous thromboembolism manifestations reported in COVID-19. Functionally, purified immunoglobulin G (IgG) extracted from patient plasma did not trigger cell apoptosis or increase barrier permeability in human vein endothelial cells. Instead, plasma IgG enhanced antibody-dependent cellular cytotoxicity mediated by patient PBMCs, a phenomenon alleviated by blocking peptide or liposome ACKR1 recombinant protein. The blocking peptide uncovered that purified IgG from COVID-19 survivors possessed potential epitopes in the N-terminal extracellular domain of ACKR1, which effectively averted antibody-dependent cellular cytotoxicity. Our findings offer insights into therapeutic development to mitigate autoantibody reactivity in blood vessels in chronic inflammation.

Mechanoresponsive ETS1 causes endothelial dysfunction and arterialization in varicose veins via NOTCH4/DLL4 signaling

Varicose veins are the most common venous disorder in humans and are characterized by hemodynamic instability due to valvular insufficiency and orthostatic lifestyle factors. It is unclear how changes in biomechanical signals cause aberrant remodeling of the vein wall. Our previous studies suggest that Notch signaling is implicated in varicose vein arterialization. In the arterial system, mechanoresponsive ETS1 is a transcriptional activator of the endothelial Notch, but its involvement in sensing disrupted venous flow and varicose vein formation has not been investigated. Here, we use human varicose veins and cultured human venous endothelial cells to show that disturbed venous shear stress activates ETS1-NOTCH4/DLL4 signaling. Notch components were highly expressed in the neointima, whereas ETS1 was upregulated in all histological layers of varicose veins. In vitro microfluidic flow-based studies demonstrate that even minute changes in venous flow patterns enhance ETS1-NOTCH4/DLL4 signaling. Uniform venous shear stress, albeit an inherently low-flow system, does not induce ETS1 and Notch proteins. ETS1 activation under altered flow was mediated primarily by MEK1/2 and, to a lesser extent, by MEK5 but was independent of p38 MAP kinase. Endothelial cell-specific ETS1 knockdown prevented disturbed flow-induced NOTCH4/DLL4 expression. TK216, an inhibitor of ETS-family, prevented the acquisition of arterial molecular identity and loss of endothelial integrity in cells exposed to the ensuing altered shear stress. We conclude that ETS1 senses blood flow disturbances and may promote venous remodeling by inducing endothelial dysfunction. Targeting ETS1 rather than downstream Notch proteins could be an effective and safe strategy to develop varicose vein therapies.

Single-Cell Analyses Offer Insights into the Different Remodeling Programs of Arteries and Veins.

Arteries and veins develop different types of occlusive diseases and respond differently to injury. The biological reasons for this discrepancy are not well understood, which is a limiting factor for the development of vein-targeted therapies. This study contrasts human peripheral arteries and veins at the single-cell level, with a focus on cell populations with remodeling potential. Upper arm arteries (brachial) and veins (basilic/cephalic) from 30 organ donors were compared using a combination of bulk and single-cell RNA sequencing, proteomics, flow cytometry, and histology. The cellular atlases of six arteries and veins demonstrated a 7.8× higher proportion of contractile smooth muscle cells (SMCs) in arteries and a trend toward more modulated SMCs. In contrast, veins showed a higher abundance of endothelial cells, pericytes, and macrophages, as well as an increasing trend in fibroblasts. Activated fibroblasts had similar proportions in both types of vessels but with significant differences in gene expression. Modulated SMCs and activated fibroblasts were characterized by the upregulation of MYH10, FN1, COL8A1, and ITGA10. Activated fibroblasts also expressed F2R, POSTN, and COMP and were confirmed by F2R/CD90 flow cytometry. Activated fibroblasts from veins were the top producers of collagens among all fibroblast populations from both types of vessels. Venous fibroblasts were also highly angiogenic, proinflammatory, and hyper-responders to reactive oxygen species. Differences in wall structure further explain the significant contribution of fibroblast populations to remodeling in veins. Fibroblasts are almost exclusively located outside the external elastic lamina in arteries, while widely distributed throughout the venous wall. In line with the above, ECM-targeted proteomics confirmed a higher abundance of fibrillar collagens in veins vs. more basement ECM components in arteries. The distinct cellular compositions and transcriptional programs of reparative populations in arteries and veins may explain differences in acute and chronic wall remodeling between vessels. This information may be relevant for the development of antistenotic therapies.

Abstract 1130: Tenascin-C In Arteriovenous Fistula Failure: Unraveling Venous Remodeling Dynamics

Background: AVF are the preferred vascular access for hemodialysis, with superior patency and lower infection rates than grafts or catheters. Nevertheless, AVF patency is reduced by both early thrombosis and NIH, culminating in diminished utilization due to one-year patency rates as low as 40-50%. Tenascin-C (TnC), an ECM glycoprotein with limited adult expression, is transiently present at sites of tissue injury and inflammation. TnC has been implicated in playing a role in the development of NIH. Hypothesis: Sustained TnC expression contributes to NIH, potentially leading to AVF failure. Methods: Female and male wild-type C57Bl/6 mice, aged 9-11 weeks, had sham surgery or AVF creation by puncturing the infrarenal aorta into the inferior vena cava (IVC) with a 25-gauge needle. Doppler ultrasound confirmed AVF presence. Tissue samples were collected for IF, WB, and qPCR. Human matched vein and AVF tissue were obtained from patients undergoing planned two-stage AVF creation surgeries and analyzed with IF. In vitro analysis of human dermal microvascular endothelial cells (HDMEC) was performed to investigate the role of TnC in thrombomodulin expression. Results: TnC expression significantly increased in the AVF by day 7, returning to baseline by day 21 and reaching negligible levels by day 42. The spatial and temporal regulation of TnC expression post-AVF creation correlated with ECM remodeling and inversely with thrombomodulin. Both mice and human studies demonstrated differential regulation of TnC and thrombomodulin in patent and occluded AVF. In HDMEC, TnC knockdown suppressed NF-kB expression and increased thrombomodulin expression, while exogenous TnC had the opposite effect. Conclusion: TnC plays a pivotal role in driving pathological inflammation, with its expression being both temporally and spatially regulated during venous remodeling post-AVF creation. Persistent TnC expression is noted in occluded mouse and human AVF, leading to decreased thrombomodulin expression and heightened thrombogenicity. Sustained TnC expression regulates the shift from physiological to pathological venous remodeling, underscoring the crucial role of the immune response in this process and highlighting potential translational therapeutic strategies.

Abstract 3092: Smooth Muscle Cell Tgf-β Receptor Knockout Improves Arteriovenous Fistula Maturation Via Attenuation Of Autophagy

Objectives: Arteriovenous fistulae (AVF) are the preferred vascular access for patients with end-stage renal disease (ESRD) but have high rates of primary failure. Models of AVF using mice with chronic kidney disease (CKD) show diminished maturation and increased failure compared to AVF using wild type mice. Since mice with CKD show increased TGF-β1 expression and activity in the AVF model, and TGF-β1 signaling can alter autophagy, we hypothesized that CKD increases autophagy during AVF maturation, whereas inhibition of the smooth muscle cell (SMC) TGF-β receptor would attenuate autophagy and promote AVF maturation. Methods: An aortocaval fistula or sham procedure was created in mice that had CKD induced by 5/6 nephrectomy (5/6 Nx) or sham nephrectomy (0/6 Nx). Myh11-CreER T2 ; Tgfbr1 fl/fl ; Tgfbr2 fl/fl ; mT/mG mice (TGFβRI II-KO) and control C57BL/6J mice were used. The diameter of the IVC was determined using ultrasound at days 0, 7, 14, and 21. AVF were harvested at day 7 or 21 for histology and immunoreactivity. Deidentified human AVF and control vein specimens were collected for analysis from second stage basilic vein transpositions. Results: In C57BL/6J mice, AVF had significantly decreased diameter (p=0.0051), increased wall thickness (p=0.0002), as well as increased immunoreactivity of collagen-1 (p=0.0163), collagen-3 (p=0.0029), TGF-β1 (p=0.0184) and fibronectin (p=0.00321) in mice with CKD compared to control mice (n=6). SMC showed increased markers of autophagy (LC3B and P62) in mice with CKD compared to control mice (LC3B, p&lt;0.0001; P62, p=0.006; n=6); similarly, autophagy makers were increased in human AVF compared with the control veins (LC3B, p=0.0023; P62, p=0.006; n=6). In SMC-TGFβR II-KO mice, AVF had significantly decreased wall thickness (p&lt;0.0001), increased diameter (p=0.0258), and decreased expression of autophagy markers (LC3B, p=0.0014; P62, p=0.0046; n=6). Conclusion: CKD increases neointimal hyperplasia that is associated with increased autophagy during AVF failure, and diminished TGF-β signaling reduces autophagy and wall thickness as well as increases AVF diameter. Suppression of SMC autophagy might be a novel therapeutic approach to improve AFV function.

Oxygenation heterogeneity facilitates spatiotemporal flow pattern visualization inside human blood vessels using photoacoustic computed tomography

Hemodynamics can be explored through various biomedical imaging techniques. However, observing transient spatiotemporal variations in the saturation of oxygen (sO2) within human blood vessels proves challenging with conventional methods. In this study, we employed photoacoustic computed tomography (PACT) to reconstruct the evolving spatiotemporal patterns in a human vein. Through analysis of the multi-wavelength photoacoustic (PA) spectrum, we illustrated the dynamic distribution within blood vessels. Additionally, we computationally rendered the dynamic process of venous blood flowing into the major vein and entering a branching vessel. Notably, we successfully recovered, in real time, the parabolic wavefront profile of laminar flow inside a deep vein in vivo—a first-time achievement. While the study is preliminary, the demonstrated capability of dynamic sO2 imaging holds promise for new applications in biology and medicine.

Training in Vascular Microsurgery: The Ex Vivo Biological Model on Domestic Turkey Leg (Meleagris gallopavo).

There are various models for practicing microsurgical anastomoses, from synthetic to ex vivo and in vivo biological ones. In this study, we present the domestic turkey (Meleagris gallopavo) as an ex vivo biological model in the practice of surgical anastomoses. In our opinion, it represents a model that is very similar to a human one, low cost, and easy to find. In fact, our study shows that the diameters of the arteries and veins used for anastomoses (tibial artery diameter: 2.5 ± 0.6 mm; tibial vein diameter: 3.5 ± 1.2 mm) are similar to those of human arteries and veins most frequently used in microsurgical free flaps. So, we believe that this animal model is a great model for microsurgical training for doctors who approach this difficult and long to learn discipline.

The Potential of Bioactive Fish Collagen Oligopeptides against Hydrogen Peroxide-Induced NIH/3T3 and HUVEC Damage: The Involvement of the Mitochondria.

Extensive in vivo investigations have demonstrated the antioxidant properties of fish collagen oligopeptides (FCOPs). One of the main causes of aging and chronic non-communicable diseases is oxidative stress. Therefore, FCOPs have a broad range of applications in illness prevention and delaying aging from the standpoint of the "food is medicine" theory. However, the mechanisms that underpin the antioxidant activity of FCOPs are not completely understood. The specific objective of this essay was to investigate the antioxidant effect of FCOPs and its possible mechanism at the cellular level. Mouse embryonic fibroblasts NIH/3T3 and human vein endothelial cells (HUVECs) were exposed to 200 µM hydrogen peroxide containing different concentrations of FCOPs for 4 h and were supplemented with different concentrations of FCOPs for 24 h. Normal growth medium without FCOPs was applied for control cells. An array of assays was used to evaluate the implications of FCOPs on cellular oxidative stress status, cellular homeostasis, inflammatory levels, and mitochondrial function. We found that FCOPs exerted a protective effect by inhibiting reactive oxygen species (ROS) production, enhancing superoxide dismutase (SOD) and endothelial nitric oxide synthase (eNOS) activities and cell viability, inhibiting cell cycle arrest in the G1 phase, suppressing interleukin-1β (IL-1β), IL-6, matrix metalloproteinase-3 (MMP-3) and intercellular adhesion molecule-1(ICAM-1) secretion, downregulating nuclear factor-kappa B (NF-κB) activity, protecting mitochondrial membrane potential, and increasing ATP synthesis and NAD+ activities in both cells. FCOPs had a stronger antioxidant impact on NIH/3T3 than on HUVECs, simultaneously increasing glutathione peroxidase (GSH-Px) activity and decreasing malondialdehyde (MDA) content in NIH/3T3. These findings indicate that FCOPs have antioxidant effects on different tissue cells damaged by oxidative stress. FCOPs were therefore found to promote cellular homeostasis, inhibit inflammation, and protect mitochondria. Meanwhile, better health outcomes will be achieved by thoroughly investigating the effective dose and intervention time of FCOPs, as the absorption efficiency of FCOPs varies in different tissue cells.

Control of Self-Winding Microrobot Using an Electromagnetic Drive System: Integration of Movable Electromagnetic Coil and Permanent Magnet.

Achieving precise control over the motion position and attitude direction of magnetic microrobots remains a challenging task in the realm of microrobotics. To address this challenge, our research team has successfully implemented synchronized control of a microrobot's motion position and attitude direction through the integration of electromagnetic coils and permanent magnets. The whole drive system consists of two components. Firstly, a stepper motor propels the delta structure, altering the position of the end-mounted permanent magnet to induce microrobot movement. Secondly, a programmable DC power supply regulates the current strength in the electromagnetic coil, thereby manipulating the magnetic field direction at the end and influencing the permanent magnet's attitude, guiding the microrobot in attitude adjustments. The microrobot used for performance testing in this study was fabricated by blending E-dent400 photosensitive resin and NdFeB particles, employing a Single-Layer 4D Printing System Using Focused Light. To address the microrobot drive system's capabilities, experiments were conducted in a two-dimensional and three-dimensional track, simulating the morphology of human liver veins. The microrobot exhibited an average speed of 1.3 mm/s (movement error ± 0.5 mm). Experimental results validated the drive system's ability to achieve more precise control over the microrobot's movement position and attitude rotation. The outcomes of this study offer valuable insights for future electromagnetic drive designs and the application of microrobots in the medical field.

Proteome of Personalized Tissue-Engineered Veins.

Vascular diseases are the largest cause of death globally and impose a major global burden on healthcare. The gold standard for treating vascular diseases is the transplantation of autologous veins, if applicable. Alternative treatments still suffer from shortcomings, including low patency, lack of growth potential, the need for repeated intervention, and a substantial risk of developing infections. The use of a vascular ECM scaffold reconditioned with the patient's own cells has shown successful results in preclinical and clinical studies. In this study, we have compared the proteomes of personalized tissue-engineered veins of humans and pigs. By applying tandem mass tag (TMT) labeling LC/MS-MS, we have investigated the proteome of decellularized (DC) veins from humans and pigs and reconditioned (RC) DC veins produced through perfusion with the patient's whole blood in STEEN solution, applying the same technology as used in the preclinical studies. The results revealed high similarity between the proteomes of human and pig DC and RC veins, including the ECM texture after decellularization and reconditioning. In addition, functional enrichment analysis showed similarities in signaling pathways and biological processes involved in the immune system response. Furthermore, the classification of proteins involved in immune response activity that were detected in human and pig RC veins revealed proteins that evoke immunogenic responses, which may lead to graft rejection, thrombosis, and inflammation. However, the results from this study imply the initiation of wound healing rather than an immunogenic response, as both systems share the same processes, and no immunogenic response was reported in the preclinical and clinical studies. Finally, our study assessed the application of STEEN solution in tissue engineering and identified proteins that may be useful for the prediction of successful transplantations.

The development of early human lymphatic vessels as characterized by lymphatic endothelial markers

Lymphatic vessel development studies in mice and zebrafish models have demonstrated that lymphatic endothelial cells (LECs) predominantly differentiate from venous endothelial cells via the expression of the transcription factor Prox1. However, LECs can also be generated from undifferentiated mesoderm, suggesting potential diversity in their precursor cell origins depending on the organ or anatomical location. Despite these advances, recapitulating human lymphatic malformations in animal models has been difficult, and considering lymphatic vasculature function varies widely between species, analysis of development directly in humans is needed. Here, we examined early lymphatic development in humans by analyzing the histology of 31 embryos and three 9-week-old fetuses. We found that human embryonic cardinal veins, which converged to form initial lymph sacs, produce Prox1-expressing LECs. Furthermore, we describe the lymphatic vessel development in various organs and observe organ-specific differences. These characterizations of the early development of human lymphatic vessels should help to better understand the evolution and phylogenetic relationships of lymphatic systems, and their roles in human disease.

HyperVein: A Hyperspectral Image Dataset for Human Vein Detection.

HyperSpectral Imaging (HSI) plays a pivotal role in various fields, including medical diagnostics, where precise human vein detection is crucial. HyperSpectral (HS) image data are very large and can cause computational complexities. Dimensionality reduction techniques are often employed to streamline HS image data processing. This paper presents a HS image dataset encompassing left- and right-hand images captured from 100 subjects with varying skin tones. The dataset was annotated using anatomical data to represent vein and non-vein areas within the images. This dataset is utilised to explore the effectiveness of dimensionality reduction techniques, namely: Principal Component Analysis (PCA), Folded PCA (FPCA), and Ward's Linkage Strategy using Mutual Information (WaLuMI) for vein detection. To generate experimental results, the HS image dataset was divided into train and test datasets. Optimum performing parameters for each of the dimensionality reduction techniques in conjunction with the Support Vector Machine (SVM) binary classification were determined using the Training dataset. The performance of the three dimensionality reduction-based vein detection methods was then assessed and compared using the test image dataset. Results show that the FPCA-based method outperforms the other two methods in terms of accuracy. For visualization purposes, the classification prediction image for each technique is post-processed using morphological operators, and results show the significant potential of HS imaging in vein detection.

The intricate cellular ecosystem of human peripheral veins as revealed by single-cell transcriptomic analysis.

The venous system has been historically understudied despite its critical roles in blood distribution, heart function, and systemic immunity. This study dissects the microanatomy of upper arm veins at the single cell level, and how it relates to wall structure, remodeling processes, and inflammatory responses to injury. We applied single-cell RNA sequencing to 4 non-diseased human veins (3 basilic, 1 cephalic) obtained from organ donors, followed by bioinformatic and histological analyses. Unsupervised clustering of 20,006 cells revealed a complex ecosystem of endothelial cell (EC) types, smooth muscle cell (SMCs) and pericytes, various types of fibroblasts, and immune cell populations. The venous endothelium showed significant upregulation of cell adhesion genes, with arteriovenous zonation EC phenotypes highlighting the heterogeneity of vasa vasorum (VV) microvessels. Venous SMCs had atypical contractile phenotypes and showed widespread localization in the intima and media. MYH11+DESlo SMCs were transcriptionally associated with negative regulation of contraction and pro-inflammatory gene expression. MYH11+DEShi SMCs showed significant upregulation of extracellular matrix genes and pro-migratory mediators. Venous fibroblasts ranging from secretory to myofibroblastic phenotypes were 4X more abundant than SMCs and widely distributed throughout the wall. Fibroblast-derived angiopoietin-like factors were identified as versatile signaling hubs to regulate angiogenesis and SMC proliferation. An abundant monocyte/macrophage population was detected and confirmed by histology, including pro-inflammatory and homeostatic phenotypes, with cell counts positively correlated with age. Ligand-receptor interactome networks identified the venous endothelium in the main lumen and the VV as a niche for monocyte recruitment and infiltration. This study underscores the transcriptional uniqueness of venous cells and their relevance for vascular inflammation and remodeling processes. Findings from this study may be relevant for molecular investigations of upper arm veins used for vascular access creation, where single-cell analyses of cell composition and phenotypes are currently lacking.

A SERS-assisted 3D organotypic microfluidic chip for in-situ visualization and monitoring breast cancer extravasation process

Extravasation, as one of the key steps in cancer metastasis, refers to the process where tumor cells escape the bloodstream by crossing the vascular endothelium and invade the targeted tissue, which accounts for the low five-year survival rate of cancer patients. Understanding the mechanism of cancer metastasis and inhibiting extravasation are crucial to improve patient prognosis. Here, a 3D organotypic microfluidic chip combined with SERS-based protein imprinted nanomaterials (SPINs) was proposed to study the extravasation process in vitro. The chip consists of a collagen gel channel and a vascular channel where human vein endothelial cells (HUVECs) and breast cancer cells are injected sequentially to induce extravasation. By comparing two subtypes of breast cancer cells (MCF-7 and MDA-MB-231), we successfully observed the difference in extravasation capabilities between two kinds of cells through fluorescence imaging. Meanwhile, thanks to the high specificity of molecular imprinting technology and the high sensitivity of surface enhanced Raman scattering (SERS), SPINs were utilized to analyze the concentration of several cancer secretions (interleukin-6 and interleukin-8) in complex biological fluid in real-time. Further, our model showed that downregulation of secretions by therapeutic drugs can inhibit the extravasation of breast cancers. This microfluidic model may pave the way for the fundamental research of the cancer metastasis and evaluating the therapeutic efficacy of potential drugs.