Embedding Biomimetic Vascular Networks via Coaxial Sacrificial Writing into Functional Tissue.

Printing human tissues and organs replete with biomimetic vascular networks is of growing interest. While it is possible to embed perfusable channels within acellular and densely cellular matrices, they do not currently possess the biomimetic architectures found in native vessels. Here, coaxial sacrificial writing into functional tissues (co-SWIFT) is developed, an embedded bioprinting method capable of generating hierarchically branching, multilayered vascular networks within both granular hydrogel and densely cellular matrices. Coaxial printheads are designed with an extended core-shell configuration to facilitate robust core-core and shell-shell interconnections between printed branching vessels during embedded bioprinting. Using optimized core-shell ink combinations, biomimetic vessels composed of a smooth muscle cell-laden shell that surrounds perfusable lumens are coaxially printed into granular matrices composed of: 1) transparent alginate microparticles, 2) sacrificial microparticle-laden collagen, or 3) cardiac spheroids derived from human induced pluripotent stem cells. Biomimetic blood vessels that exhibit good barrier function are produced by seeding these interconnected lumens with a confluent layer of endothelial cells. Importantly, it is found that co-SWIFT cardiac tissues mature under perfusion, beat synchronously, and exhibit a cardio-effective drug response in vitro. This advance opens new avenues for the scalable biomanufacturing of vascularized organ-specific tissues for drug testing, disease modeling, and therapeutic use.

Impact of low-to moderate-intensity exercise training on the mRNA expression of purine receptors across various vessels in SHR.

OBJECTIVE: In this study, we developed an exercise training protocol for assessing both blood pressure dynamics and mRNA expression levels of purine receptors in various vascular tissues during physical activity. The objective is to assess the impact of exercise training on blood pressure regulation in spontaneously hypertensive rats (SHR) and purine receptors in vascular tissues. METHODS: Wistar Kyoto (WKY) and SHR rats were randomly allocated into sedentary (Sed) and exercise training (ExT) groups. Rats in the Sed groups were allowed unrestricted movement, whereas those in the ExT groups underwent a 16-week regimen of low- to moderate-intensity treadmill exercise. Throughout the intervention period, blood pressure measurements and body weight recordings were conducted. Additionally, mRNA expressions of purine receptors P2X1, P2Y1, and P2Y2 in renal artery (RA), internal carotid artery (Int), thoracic aorta (Aor), and caudal artery (Cau) tissues were assessed. RESULTS: In the Sed group, body weight of SHR rats was observed to be lower compared to the three other groups. Over the course of the exercise regimen, blood pressure in the ExT group of SHR rats reduced gradually, converging towards levels similar to those observed in WKY rats by the conclusion of the exercise period. Regarding mRNA expression patterns of P2X1 receptors across the four blood vessels, WKY and SHR rats demonstrated similar sequences, consistently displaying the highest expression levels in the Cau. Conversely, mRNA expressions of P2Y1 and P2Y2 receptors exhibited distinct sequences across the four blood vessels in both WKY and SHR rats. Notably, compared to the Sed group of WKY rats, mRNA expression of P2X1 receptor in the Int of SHR rats revealed an increase, while expressions in the Aor of WKY rats and the Cau of SHR rats decreased following exercise. Expression of P2Y1 receptor mRNA decreased across all four types of blood vessels in SHR rats. Post-exercise, P2Y1 receptor mRNA expression increased in the Aor, decreased in the Cau of WKY rats, and increased in the Int and renal artery (RA) of SHR rats. Conversely, expressions of P2Y2 receptor mRNA decreased in the Int and Aor of SHR rats. Except for the Aor of WKY rats, expressions of P2Y2 receptor mRNA increased in the other arteries of both rat types following exercise. CONCLUSION: Differences in the distribution of purine receptor subtypes among distinct arterial segments in both WKY and SHR rats were observed. Exercise training was found to enhance mRNA expression levels of P2Y receptors in these rat models. This finding implies that exercise training might reduce hypertension in SHR rats by bolstering the purinergic relaxation response.

Evaluation of the mesenteric arterial vasculature by computed tomography angiography and its implications for colorectal cancer surgery.

Objective: To determine the branching patterns of the inferior mesenteric artery (IMA) and to describe the clinical applicability of computed tomography (CT) angiography in the evaluation of these vessels to facilitate the planning of colorectal cancer surgery. Materials and Methods: We included 100 patients who underwent CT angiography of the abdomen and pelvis. The branching patterns of the IMA were examined and classified as type 1 (bifurcated), including 1A (sigmoid and left colic arteries arising from a common trunk), 1B (sigmoid and superior rectal arteries arising from a common trunk) and 1C (sigmoid arteries arising from both trunks); type 2 (trifurcated); and type 3 (no left colic branch). Results: Among the 100 patients evaluated, we found the variant to be type 1A in 9%, type 1B in 47%, type 1C in 24%, type 2 in 16%, and type 3 in 4%. Conclusion: Preoperative CT angiography for evaluating the IMA branching pattern could inform decisions regarding the surgical approach to colorectal cancer.

Objetivo: Determinar os padrões de ramificação da artéria mesentérica inferior (AMI) e descrever a aplicabilidade clínica da angiografia por tomografia computadorizada na avaliação desses vasos na elaboração das estratégias pré-operatórias de cirurgia de câncer colorretal. Materiais e Métodos: Foram incluídos 100 pacientes submetidos a angiografia por tomografia computadorizada abdominal e pélvica. Os padrões de ramificação da AMI foram examinados e classificados como tipo 1 (bifurcado), incluindo 1A (artérias sigmoide e cólica esquerda originando-se de um tronco comum), 1B (artérias sigmoide e retal superior originando-se de um tronco comum) e 1C (artérias sigmoide originando-se de ambos os troncos); tipo 2 (trifurcado); e tipo 3 (sem ramo cólico esquerdo). Resultados: Do total de participantes incluídos no estudo, a variante do tipo 1A foi observada em 9%, a do tipo 1B em 47%, e a do tipo 1C em 24%. Com relação à variante tipo 2, esta foi observada em 16% dos pacientes, e a do tipo 3, em 4% dos casos.Conclusão O uso da angiografia por tomografia computadorizada pré-operatória para avaliar o padrão de ramificação da AMI pode ajudar a escolher a abordagem cirúrgica no câncer colorretal.

Safety and effectiveness of using Disposable Ultrasonic shears to coagulate 5-7 mm blood vessels: protocol for a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial.

BACKGROUND: The ultrasonic scalpel is widely used during surgery. It is safe and effective to close the pulmonary artery branch vessels of 7 mm or below with an ultrasonic energy device as reported. However, there have been no multicenter randomized clinical trial to assess the safety and effectiveness of using ultrasonic scalpel to coagulate 5-7 mm blood vessels in thoracic surgery. METHODS: This is a prospective, multicenter, randomized, parallel controlled, non-inferiority clinical trial. A total of 144 eligible patients planning to undergo lung or esophageal surgery will be randomly allocated to the experimental group and the control group. The investigational product (Disposable Ultrasonic Shears manufactured by Reach Surgical, Inc.) and the control product (Harmonic Ace + 7, 5 mm Diameter Shears with Advanced Hemostasis) will be used in each group. The primary endpoint is the success rate of coagulating target blood vessels during surgery. Secondary endpoints include postoperative rebleeding, intraoperative bleeding volume, drainage volume, surgical duration, etc. Postoperative follow-up before and after discharge will be performed. DISCUSSION: This clinical trial aims to evaluate the safety and effectiveness of using the investigational product (Disposable Ultrasonic Shears manufactured by Reach Surgical, Inc.) and that of the control product (Harmonic Ace + 7, 5 mm Diameter Shears with Advanced Hemostasis) to coagulate 5-7 mm blood vessels in thoracic surgery. TRIAL REGISTRATION: ClinicalTrials.gov: NCT06002737. The trial was prospectively registered on 16 August 2023, https://www. CLINICALTRIALS: gov/study/NCT06002737 .

A feasible way to explore real blood vessels thermal responses to laser irradiation by combing optical clearing and the reflectance spectra measurements: animal experiment study.

Laser therapy has been widely used to treat port-wine stains (PWS) and other cutaneous vascular lesions via selective photothermolysis. Animal models are a valuable tool for investigating thermal responses beneath the skin. However, in previous animal experiments, such as the dorsal skin chamber model, one side of the skin was removed, resulting in the loss of mechanical support for the target blood vessel. In this study, the optical clearing technique was applied to the dorsal skin, allowing direct observation of real thermal responses within the tissue without removing the covering skin. The target blood vessels were irradiated with a pulsed 1064 nm Nd: YAG laser. The corresponding thermal responses were recorded using a CCD camera. Additionally, variations in skin reflectance spectra were measured before and after laser irradiation. Due to the optical clearing and reflectance spectra measurement, vessel responses such as contraction, reperfusion, and full occlusion were correlated with specific variation patterns in reflectance spectral signals.

Microvascular Changes during Viral Infections: A Systematic Review of Studies Using Retinal Vessel Diameter Assessments.

Viral infection frequently affects the cardiovascular system, and vascular disturbances in patients can lead to health complications. One essential component of the cardiovascular system that is vulnerable to the inflammatory effects of viral infections is the microcirculatory system. As a suitable and practical non-invasive method to assess the structure and function of the retinal microcirculation, a proxy for the microcirculatory system, retinal fundus imaging can be used. We examined the impact of viral infections on retinal vessel diameters and performed a systematic analysis of the literature. Our search was carried out on PubMed using predefined search queries. After a methodological filtering process, we were able to reduce the corpus of 363 publications to 16 studies that met the search parameters. We used a narrative review style to summarise the observations. Six studies covered COVID-19, seven described HIV, and three were included in the subgroup called others, covering viruses, such as Dengue Fever and Crimean-Congo Haemorrhagic Fever. Analysis of the literature showed that viral infections are associated with alterations in the retinal vessels' vasoactivity. COVID-19 and other infections cause inflammation-associated the vasodilatation of microvasculature as a short-term effect of the infection. Long COVID-19 as well as HIV are the cause of chronic inflammation impacting microvascular morphology via retinal vessel diameter narrowing. The review emphasises the importance of the understudied area of viral infections' effects on retinal microcirculation. Continuous research in this area is needed to further verify retinal fundus imaging as an innovative tool for the optimal diagnosis of microvascular changes. As changes in the microvasculature precede changes in bigger arteries, the early detection of microvascular changes can go a long way in reducing the morbidity and mortality associated with cardiovascular diseases.

Imaging light fluence in blood vessels by combining photoacoustic fluctuation imaging and ultrasound power doppler.

Numerous optical biomedical imaging or therapeutic modalities suffer from unknown light fluence distribution at depths. Photoacoustic (PA) imaging enables imaging of blood vessels. At the scale of the acoustic resolution, PA imaging probes the product between the fluence and effective optical absorption that depends on the size or density of blood vessels. In the case of unresolved vessels, fluence and absorption can not be decoupled using PA imaging alone without the use of inverse problems. Thus, we propose combining two modalities that are sensitive to blood vessels to directly image fluence maps within vascularized areas, including in unresolved vessels. To achieve fluence imaging, the combination of photoacoustic fluctuation (PAFI) and Ultrasound Power Doppler (UPD) images is considered. After exposing a new theoretical expression of the UPD image, we establish a fluence imaging method giving quantitative fluence in blood vessels. This method universally applies to arbitrary hematocrit and multi-scale vessel imaging. Using a spherical sparse array, we demonstrate 3D fluence imaging within blood vessels in simulation and experiments which is not possible with PAFI alone. Fluence imaging involves resolution compensation with a PSF filter that is compared to alternative simpler corrections. Overall, we show that combining PAFI and UPD has the potential for real-time light dosimetry or could enhance quantitative inverse problems in photoacoustic imaging.

Identification of cortical arteries and veins in awake mice using two-photon microscopy.

Distinguishing arteries from veins in the cerebral cortex is critical for studying hemodynamics under pathophysiological conditions, which plays an important role in the diagnosis and treatment of various vessel-related diseases. However, due to the complexity of the cerebral vascular network, it is challenging to identify arteries and veins in vivo. Here, we demonstrate an artery-vein separation method that employs a combination of multiple scanning modes of two-photon microscopy and a custom-designed stereoscopic fixation device for mice. In this process, we propose a novel method for determining the line scanning direction, which allows us to determine the blood flow directions. The vasculature branches have been identified using an optimized z-stack scanning mode, followed by the separation of blood vessel types according to the directions of blood flow and branching patterns. Using this strategy, the penetrating arterioles and penetrating venules in awake mice could be accurately identified and the type of cerebral thrombus has been also successfully isolated without any empirical knowledge or algorithms. Our research presents a new, more accurate, and efficient method for cortical artery-vein separation in awake mice, providing a useful strategy for the application of two-photon microscopy in the study of cerebrovascular pathophysiology.

Pia-FLOW: Deciphering hemodynamic maps of the pial vascular connectome and its response to arterial occlusion.

The pial vasculature is the sole source of blood supply to the neocortex. The brain is contained within the skull, a vascularized bone marrow with a unique anatomical connection to the brain meninges. Recent developments in tissue clearing have enabled detailed mapping of the entire pial and calvarial vasculature. However, what are the absolute flow rate values of those vascular networks? This information cannot accurately be retrieved with the commonly used bioimaging methods. Here, we introduce Pia-FLOW, a unique approach based on large-scale transcranial fluorescence localization microscopy, to attain hemodynamic imaging of the whole murine pial and calvarial vasculature at frame rates up to 1,000 Hz and spatial resolution reaching 5.4 µm. Using Pia-FLOW, we provide detailed maps of flow velocity, direction, and vascular diameters which can serve as ground-truth data for further studies, advancing our understanding of brain fluid dynamics. Furthermore, Pia-FLOW revealed that the pial vascular network functions as one unit for robust allocation of blood after stroke.

Decellularized, Heparinized Small-Caliber Tissue-Engineered "Biological Tubes" for Allograft Vascular Grafts.

There remains a lack of small-caliber tissue-engineered blood vessels (TEBVs) with wide clinical use. Biotubes were developed by electrospinning and in-body tissue architecture (iBTA) technology to prepare small-caliber TEBVs with promising applications. Different ratios of hybrid fibers of poly(l-lactic-co-ε-caprolactone) (PLCL) and polyurethane (PU) were obtained by electrospinning, and the electrospun tubes were then implanted subcutaneously in the abdominal area of a rabbit (as an in vivo bioreactor). The biotubes were harvested after 4 weeks. They were then decellularized and cross-linked with heparin. PLCL/PU electrospun vascular tubes, decellularized biotubes (D-biotubes), and heparinized combined decellularized biotubes (H + D-biotubes) underwent carotid artery allograft transplantation in a rabbit model. Vascular ultrasound follow-up and histological observation revealed that the biotubes developed based on electrospinning and iBTA technology, after decellularization and heparinization cross-linking, showed a better patency rate, adequate mechanical properties, and remodeling ability in the rabbit model. IBTA technology caused a higher patency, and the heparinization cross-linking process gave the biotubes stronger mechanical properties.

[Retrospective study on the impact of penile corpus cavernosum injection test on penile vascular function].

OBJECTIVE: To investigate the impact of age, various hormonal levels, and biochemical markers on penile cavernous body vascular function in patients with erectile dysfunction (ED). Me-thods: A retrospective analysis of clinical data from male patients with ED who underwent color duplex Doppler ultrasonography (CDDU) and intracavernosal injection test (ICI) at the Reproductive Medicine Center of Peking University Third Hospital from January 2020 to August 2023. Data were managed and processed using SPSS 29.0, and a multivariable Logistic regression analysis was conducted. RESULTS: A total of 700 ED patients were included, with 380 showing negative ICI results and 320 positive. In the study, 84 patients had a peak systolic velocity (PSV) < 25 cm/s, while 616 had PSV≥25 cm/s; 202 patients had end-diastolic velocity (EDV)>5 cm/s, and 498 had EDV≤5 cm/s. 264 patients had abnormal PSV and/or EDV results, and 436 had normal results for both. Patients with vascular ED had significantly lower estrogen levels (t=-3.546, P < 0.001), lower testosterone levels (t=-2.089, P=0.037), and a higher rate of hyperglycemia (χ2=12.772, P=0.002) compared with those with non-vascular ED. The patients with arterial ED were older (t=3.953, P < 0.001), had a higher rate of hyperglycemia (χ2=9.518, P=0.009), and a higher estrogen/testosterone ratio (t=2.330, P=0.020) compared with those with non-arterial ED. The patients with mixed arteriovenous ED had higher age (t=3.567, P < 0.001), lower testosterone levels (t=-2.288, P=0.022), a higher rate of hyperglycemia (χ2=12.877, P=0.002), and a larger estrogen/testosterone ratio (t=2.096, P=0.037) compared with those with normal findings. Multifactorial Logistic regression analysis indicated that higher levels of estrogen were a protective factor for vascular ED (OR=1.009, 95%CI: 1.004-1.014), and glucose≥7.0 mmol/L was a risk factor (OR=0.381, 95%CI: 0.219-0.661). Older age was a risk factor for arterial ED (OR=0.960, 95%CI: 0.938-0.982). Additionally, older age (OR=0.976, 95%CI: 0.958-0.993) and glucose levels of 5.6-6.9 mmol/L (OR=0.591, 95%CI: 0.399-0.876) were also risk factors for mixed arterio-venous ED. CONCLUSION: Hyperglycemia and aging may impair penile cavernous body vascular function, while higher levels of estrogen may have a protective effect on it.

Case report: A huge retroperitoneal solitary fibrous tumor closely related to the external iliac vessels misdiagnosed as an ovarian tumor.

Background: Solitary fibrous tumor (SFT) is a rare soft tissue tumor originating from mesenchymal cells. Thus far, there have been no reported cases of SFT closely related to the iliac vessels. Case presentation: An elderly woman was found to have had a lower abdominal mass for more than 20 years. The enhanced computerized tomography (CT) showed a progressively enhanced hypervascular mass. The external iliac blood vessels were closely related to the mass, which was misdiagnosed as an ovarian tumor. During laparotomy, the external iliac vein was seen to penetrate the tumor, and the external iliac artery was seen to penetrate the tumor capsule. The retroperitoneal tumor was diagnosed during the operation. The surgical plan of complete tumor resection, severing of the external iliac arteries and veins, and blood vessel replacement was implemented. Pathological immunohistochemistry showed positive results for STAT6 and CD34, confirming the diagnosis of giant retroperitoneal SFT. The risk is classified as high and requires long-term follow-up. There has been no local recurrence or distant metastasis almost 1 year after surgery. Conclusion: The incidence of giant retroperitoneal SFT is rare, and the diagnosis can be confirmed through preoperative imaging examination and pathological examination. If the SFT capsule is intact, there is a chance of surgical resection. For SFTs that are penetrated by the iliac blood vessels, adequate preparation must be made before the surgery is performed. Removing the tumor and the iliac blood vessels at the corresponding site and then replacing it with artificial blood vessels is a feasible method with less risk of bleeding. In this case, imaging showed a progressively enhancing hypervascular mass in the lower abdomen, which was related to blood vessels. Preoperative biopsy and pathological testing can confirm the diagnosis. Neoadjuvant therapy or interventional therapy before surgery can shrink the tumor, making the surgical procedure relatively easy with less risk of bleeding.

Retinal Blood Vessel Formation in the Macula Following Intravitreal Ranibizumab Injection for Aggressive Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. Recently, anti-vascular endothelial growth factor (VEGF) drugs have been widely used for ROP to inhibit abnormal retinal angiogenesis. However, there is a concern that such drugs potentially also affect normal retinal vascular development. We report a case of blood vessel growth across the macula after anti-VEGF treatment for zone I aggressive ROP. A 25-week-old female infant was administered 0.2 mg of ranibizumab for bilateral aggressive ROP in both eyes at 33 weeks of postmenstrual age. Under normal development, retinal blood vessels do not grow into the center of the future macular region. After five weeks, however, a horizontal blood vessel sprouted from the optic disc and extended across the macula in the right eye. The blood vessel ran straight to the vascular-avascular juncture by 41 weeks of postmenstrual age during the follow-up period. While the focus has been on arresting retinal vascular development through VEGF inhibition, anti-VEGF treatment may induce vascular abnormalities in patients with severe ROP. Infants with retinal vascular abnormalities should be carefully monitored for their visual prognosis.

Simultaneous sealing and bisection of porcine renal blood vessels, ex vivo, using a continuous-wave, infrared diode laser at 1470 nm.

Electrosurgical and ultrasonic devices are used in surgical procedures for hemostatic sealing and bisection of vascular tissues. Previous benchtop studies alternatively demonstrated successful infrared laser sealing and cutting of blood vessels, in a sequential, two-step approach. This study describes a smaller, laparoscopic device compatible design, and simultaneous approach to sealing and bisection of vessels, with potential optical feedback. A 1470-nm infrared diode laser sealed and bisected 40 porcine renal arteries, ex vivo. A reciprocating, side-firing, optical fiber, housed in a transparent square quartz optical chamber (2.7 × 2.7 × 25 mm outer dimensions), delivered laser energy over an 11 mm scan length, with a range of incident powers (41-59 W) and treatment times (5-21 s). Vessel diameters ranged from 2.5 to 4.8 mm. Vessel burst pressure measurements were performed on each cut end (n = 80) with success indicated by pressures exceeding 360 mmHg. All vessel ends were successfully sealed and bisected (80/80). The highest incident power, 59 W, yielded short treatment times of 5-6 s. Peak temperatures on the external chamber surface reached 103 oC. Time to cool down to body temperature measured 37 s. Infrared lasers simultaneously seal and bisect blood vessels, with treatment times comparable to, and temperatures and cooling times lower than reported for conventional devices. Future work will focus on integrating the fiber and chamber into a standard 5-mm-outer-diameter laparoscopic device. Customization of fiber scan length to match vessel size may also reduce laser energy deposition, enabling lower peak temperatures, treatment times, and cooling times.

Primitive macrophages enable long-term vascularization of human heart-on-a-chip platforms.

The intricate anatomical structure and high cellular density of the myocardium complicate the bioengineering of perfusable vascular networks within cardiac tissues. In vivo neonatal studies highlight the key role of resident cardiac macrophages in post-injury regeneration and angiogenesis. Here, we integrate human pluripotent stem-cell-derived primitive yolk-sac-like macrophages within vascularized heart-on-chip platforms. Macrophage incorporation profoundly impacted the functionality and perfusability of microvascularized cardiac tissues up to 2 weeks of culture. Macrophages mitigated tissue cytotoxicity and the release of cell-free mitochondrial DNA (mtDNA), while upregulating the secretion of pro-angiogenic, matrix remodeling, and cardioprotective cytokines. Bulk RNA sequencing (RNA-seq) revealed an upregulation of cardiac maturation and angiogenesis genes. Further, single-nuclei RNA sequencing (snRNA-seq) and secretome data suggest that macrophages may prime stromal cells for vascular development by inducing insulin like growth factor binding protein 7 (IGFBP7) and hepatocyte growth factor (HGF) expression. Our results underscore the vital role of primitive macrophages in the long-term vascularization of cardiac tissues, offering insights for therapy and advancing heart-on-a-chip technologies.

Micro/nano-plastics impacts in cardiovascular systems across species.

The widespread presence of microplastics and nanoplastics (MPs/NPs) in the environment has become a critical public health issue due to their potential to infiltrate and affect various biological systems. Our review is crucial as it consolidates current data and provides a comprehensive analysis of the cardiovascular impacts of MPs/NPs across species, highlighting significant implications for human health. By synthesizing findings from studies on aquatic and terrestrial organisms, including humans, this review offers insights into the ubiquity of MPs/NPs and their pathophysiological roles in cardiovascular systems. We demonstrated that exposure to MPs/NPs is linked to various cardiovascular ailments such as thrombogenesis, vascular damage, and cardiac impairments in model organisms, which likely extrapolate to humans. Our review critically evaluated methods for detecting MPs/NPs in biological tissues, assessing their toxicity, and understanding their behaviour within the vasculature. These findings emphasise the urgent need for targeted public health strategies and enhanced regulatory measures to mitigate the impacts of MP/NP pollution. Furthermore, the review underlined the necessity of advancing research methodologies to explore long-term effects and potential intergenerational consequences of MP/NP exposure. By mapping out the intricate links between environmental exposure and cardiovascular risks, our work served as a pivotal reference for future research and policymaking aimed at curbing the burgeoning threat of plastic pollution.

Endothelial Cell Dysfunction: Onset, Progression, and Consequences.

Endothelial cell dysfunction is a complex process involving various causes, early and late events, and subsequent consequences. This review provides an overview of each aspect and outlines therapeutic interventions targeting these stages. Causes of endothelial dysfunction encompass a spectrum of risk factors including hypertension, diabetes, smoking, obesity, inflammation, oxidative stress, and genetic predispositions. Early events such as endothelial activation, inflammatory response, and dysregulated vasomotor tone precede late events like oxidative stress, endothelial apoptosis, and microvascular rarefaction. The consequences include endothelial remodelling, neovascularization, organ dysfunction, and clinical manifestations, highlighting the diverse impacts across multiple systems. While depicted linearly, the progression of endothelial dysfunction is dynamic, influenced by various factors such as the underlying cause and affected vascular bed. Understanding these dynamics is crucial for tailoring therapeutic interventions, ranging from lifestyle modifications to targeted therapies, to address the underlying causes and effects effectively. Here we provide comprehensive understanding of endothelial cell dysfunction that is essential for developing strategies to mitigate the impact of this dysregulation on health and cardiovascular diseases progression.

Unsupervised Segmentation of 3D Microvascular Photoacoustic Images Using Deep Generative Learning.

Mesoscopic photoacoustic imaging (PAI) enables label-free visualization of vascular networks in tissues with high contrast and resolution. Segmenting these networks from 3D PAI data and interpreting their physiological and pathological significance is crucial yet challenging due to the time-consuming and error-prone nature of current methods. Deep learning offers a potential solution; however, supervised analysis frameworks typically require human-annotated ground-truth labels. To address this, an unsupervised image-to-image translation deep learning model is introduced, the Vessel Segmentation Generative Adversarial Network (VAN-GAN). VAN-GAN integrates synthetic blood vessel networks that closely resemble real-life anatomy into its training process and learns to replicate the underlying physics of the PAI system in order to learn how to segment vasculature from 3D photoacoustic images. Applied to a diverse range of in silico, in vitro, and in vivo data, including patient-derived breast cancer xenograft models and 3D clinical angiograms, VAN-GAN demonstrates its capability to facilitate accurate and unbiased segmentation of 3D vascular networks. By leveraging synthetic data, VAN-GAN reduces the reliance on manual labeling, thus lowering the barrier to entry for high-quality blood vessel segmentation (F1 score: VAN-GAN vs. U-Net = 0.84 vs. 0.87) and enhancing preclinical and clinical research into vascular structure and function.

Molecular profiling of frontal and occipital subcortical white matter hyperintensities in Alzheimer's disease.

White matter hyperintensities (WMHs) are commonly detected on T2-weighted magnetic resonance imaging (MRI) scans, occurring in both typical aging and Alzheimer's disease. Despite their frequent appearance and their association with cognitive decline, the molecular factors contributing to WMHs remain unclear. In this study, we investigated the transcriptomic profiles of two commonly affected brain regions with coincident AD pathology-frontal subcortical white matter (frontal-WM) and occipital subcortical white matter (occipital-WM)-and compared with age-matched healthy controls. Through RNA-sequencing in frontal- and occipital-WM bulk tissues, we identified an upregulation of genes associated with brain vasculature function in AD white matter. To further elucidate vasculature-specific transcriptomic features, we performed RNA-seq analysis on blood vessels isolated from these white matter regions, which revealed an upregulation of genes related to protein folding pathways. Finally, comparing gene expression profiles between AD individuals with high- versus low-WMH burden showed an increased expression of pathways associated with immune function. Taken together, our study characterizes the diverse molecular profiles of white matter changes in AD compared to normal aging and provides new mechanistic insights processes underlying AD-related WMHs.