Vessel Pathology Research Articles

Engineering Smooth Muscle to Understand Extracellular Matrix Remodeling and Vascular Disease

The vascular smooth muscle is vital for regulating blood pressure and maintaining cardiovascular health, and the resident smooth muscle cells (SMCs) in blood vessel walls rely on specific mechanical and biochemical signals to carry out these functions. Any slight change in their surrounding environment causes swift changes in their phenotype and secretory profile, leading to changes in the structure and functionality of vessel walls that cause pathological conditions. To adequately treat vascular diseases, it is essential to understand how SMCs crosstalk with their surrounding extracellular matrix (ECM). Here, we summarize in vivo and traditional in vitro studies of pathological vessel wall remodeling due to the SMC phenotype and, conversely, the SMC behavior in response to key ECM properties. We then analyze how three-dimensional tissue engineering approaches provide opportunities to model SMCs’ response to specific stimuli in the human body. Additionally, we review how applying biomechanical forces and biochemical stimulation, such as pulsatile fluid flow and secreted factors from other cell types, allows us to study disease mechanisms. Overall, we propose that in vitro tissue engineering of human vascular smooth muscle can facilitate a better understanding of relevant cardiovascular diseases using high throughput experiments, thus potentially leading to therapeutics or treatments to be tested in the future.

Blood-brain barrier leakage and perivascular inflammation in cerebral amyloid angiopathy.

Cerebral amyloid angiopathy is a small vessel disease associated with cortical microbleeds and lobar intracerebral haemorrhage due to amyloid-β deposition in the walls of leptomeningeal and cortical arterioles. The mechanisms of cerebral amyloid angiopathy–related haemorrhage remain largely unknown. Recent work has demonstrated that ruptured blood vessels have limited (or no) amyloid-β at the site of bleeding and evidence of local vascular remodelling. We hypothesized that blood–brain barrier leakage and perivascular inflammation may be involved in this remodelling process. This study examined cortical arterioles at various stages of cerebral amyloid angiopathy–related vascular pathology (without evidence of microhaemorrhage) in autopsy tissue from seven cases with definite cerebral amyloid angiopathy. We included temporo-occipital sections with microbleeds guided by ex vivo MRI from two cases with severe cerebral amyloid angiopathy and systematically sampled occipital sections from five consecutive cases with varying cerebral amyloid angiopathy severity. Haematoxylin and eosin stains and immunohistochemistry against amyloid-β, fibrin(ogen), smooth muscle actin, reactive astrocytes (glial fibrillary acidic protein) and activated microglia (cluster of differentiation 68) were performed. Arterioles were graded using a previously proposed scale of individual vessel cerebral amyloid angiopathy severity, and a blinded assessment for blood–brain barrier leakage, smooth muscle actin and perivascular inflammation was performed. Blood–brain barrier leakage and smooth muscle actin loss were observed in significantly more vessels with mild amyloid-β deposition (Grade 1 vessels; P = 0.044 and P = 0.012, respectively) as compared to vessels with no amyloid-β (Grade 0), and blood–brain barrier leakage was observed in 100% of vessels with evidence of vessel remodelling (Grades 3 and 4). Perivascular inflammation in the form of reactive astrocytes and activated microglia was observed predominantly surrounding arterioles at later stages of vessel pathology (Grades 2–4) and consistently around vessels with the same morphological features as ruptured vessel segments (Grade 4). These findings suggest a role for blood–brain barrier leakage and perivascular inflammation leading to arteriolar remodelling and haemorrhage in cerebral amyloid angiopathy, with early blood–brain barrier leakage as a potential trigger for subsequent perivascular inflammation.

Retinal Laser Photocoagulation

Background: Panretinal photocoagulation (PRP) is the standard gold therapy to prevent vision loss in severe non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR).Contents: Photocoagulation is a therapeutic technique using a solid light source to coagulate tissue. This light energy is absorbed by the retinal tissue and converted into thermal energy. This energy then causes the abnormal blood vessels in the retina to shrink and disappear. It takes approximately 6-8 weeks for complete shrinkage of blood vessels.Conclusion: Laser retinal photocoagulation is the standard therapy in diabetic retinopathy patients. By causing thermal lesions of the pathological retinal vessels, the expected outcome can be achieved in 2-3 months of therapy.

BV-GAN: 3D time-of-flight magnetic resonance angiography cerebrovascular vessel segmentation using adversarial CNNs.

Purpose: Cerebrovascular vessel segmentation is a key step in the detection of vessel pathology. Brain time-of-flight magnetic resonance angiography (TOF-MRA) is a main method used clinically for imaging of blood vessels using magnetic resonance imaging. This method is primarily used to detect narrowing, blockage of the arteries, and aneurysms. Despite its importance, TOF-MRA interpretation relies mostly on visual, subjective assessment performed by a neuroradiologist and is mostly based on maximum intensity projections reconstruction of the three-dimensional (3D) scan, thus reducing the acquired spatial resolution. Works tackling the central problem of automatically segmenting brain blood vessels typically suffer from memory and imbalance related issues. To address these issues, the spatial context of the segmentation consider by neural networks is typically restricted (e.g., by resolution reduction or analysis of environments of lower dimensions). Although efficient, such solutions hinder the ability of the neural networks to understand the complex 3D structures typical of the cerebrovascular system and to leverage this understanding for decision making. Approach: We propose a brain-vessels generative-adversarial-network (BV-GAN) segmentation model, that better considers connectivity and structural integrity, using prior based attention and adversarial learning techniques. Results: For evaluations, fivefold cross-validation experiments were performed on two datasets. BV-GAN demonstrates consistent improvement of up to 10% in vessel Dice score with each additive designed component to the baseline state-of-the-art models. Conclusions: Potentially, this automated 3D-approach could shorten analysis time, allow for quantitative characterization of vascular structures, and reduce the need to decrease resolution, overall improving diagnosis cerebrovascular vessel disorders.

Effect of pulsed field ablation on solid tumor cells and microenvironment.

Pulsed field ablation can increase membrane permeability and is an emerging non-thermal ablation. While ablating tumor tissues, electrical pulses not only act on the membrane structure of cells to cause irreversible electroporation, but also convert tumors into an immune active state, increase the permeability of microvessels, inhibit the proliferation of pathological blood vessels, and soften the extracellular matrix thereby inhibiting infiltrative tumor growth. Electrical pulses can alter the tumor microenvironment, making the inhibitory effect on the tumor not limited to short-term killing, but mobilizing the collective immune system to inhibit tumor growth and invasion together.

Cellular mechanisms of oligoclonal vascular smooth muscle cell expansion in cardiovascular disease.

Quiescent, differentiated adult vascular smooth muscle cells (VSMCs) can be induced to proliferate and switch phenotype. Such plasticity underlies blood vessel homeostasis and contributes to vascular disease development. Oligoclonal VSMC contribution is a hallmark of end-stage vascular disease. Here, we aim to understand cellular mechanisms underpinning generation of this VSMC oligoclonality. We investigate the dynamics of VSMC clone formation using confocal microscopy and single-cell transcriptomics in VSMC-lineage-traced animal models. We find that activation of medial VSMC proliferation occurs at low frequency after vascular injury and that only a subset of expanding clones migrate, which together drives formation of oligoclonal neointimal lesions. VSMC contribution in small atherosclerotic lesions is typically from one or two clones, similar to observations in mature lesions. Low frequency (<0.1%) of clonal VSMC proliferation is also observed in vitro. Single-cell RNA-sequencing revealed progressive cell state changes across a contiguous VSMC population at onset of injury-induced proliferation. Proliferating VSMCs mapped selectively to one of two distinct trajectories and were associated with cells showing extensive phenotypic switching. A proliferation-associated transitory state shared pronounced similarities with atypical SCA1+ VSMCs from uninjured mouse arteries and VSMCs in healthy human aorta. We show functionally that clonal expansion of SCA1+ VSMCs from healthy arteries occurs at higher rate and frequency compared with SCA1- cells. Our data suggest that activation of proliferation at low frequency is a general, cell-intrinsic feature of VSMCs. We show that rare VSMCs in healthy arteries display VSMC phenotypic switching akin to that observed in pathological vessel remodelling and that this is a conserved feature of mouse and human healthy arteries. The increased proliferation of modulated VSMCs from healthy arteries suggests that these cells respond more readily to disease-inducing cues and could drive oligoclonal VSMC expansion.

Distinct Brain Proteomic Signatures in Cerebral Small Vessel Disease Rat Models of Hypertension and Cerebral Amyloid Angiopathy.

Cerebral small vessel diseases (CSVDs) are prominent contributors to vascular cognitive impairment and dementia and can arise from a range of etiologies. Cerebral amyloid angiopathy (CAA) and hypertension (HTN), both prevalent in the elderly population, lead to cerebral microhemorrhages, macrohemorrhages, and white matter damage. However, their respective underlying mechanisms and molecular events are poorly understood. Here, we show that the transgenic rat model of CAA type 1 (rTg-DI) exhibits perivascular inflammation that is lacking in the spontaneously hypertensive stroke-prone (SHR-SP) rat model of HTN. Alternatively, SHR-SP rats display notable dilation of arteriolar perivascular spaces. Comparative proteomics analysis revealed few shared altered proteins, with key proteins such as ANXA3, H2A, and HTRA1 unique to rTg-DI rats, and Nt5e, Flot-1 and Flot-2 unique to SHR-SP rats. Immunolabeling confirmed that upregulation of ANXA3, HTRA1, and neutrophil extracellular trap proteins were distinctly associated with rTg-DI rats. Pathway analysis predicted activation of TGF-β1 and TNFα in rTg-DI rat brain, while insulin signaling was reduced in the SHR-SP rat brain. Thus, we report divergent protein signatures associated with distinct cerebral vessel pathologies in the SHR-SP and rTg-DI rat models and provide new mechanistic insight into these different forms of CSVD.

A systematic review and meta-analysis of preanalytical factors and methodological differences influencing the measurement of circulating vascular endothelial growth factor.

BackgroundIntraocular treatment with antibodies targeting vascular endothelial growth factor (anti-VEGF) inhibits pathological vessel growth in adults and preterm infants. Recently, concerns regarding the impact of anti-VEGF treatment on systemic VEGF levels in preterm infants have been raised. Earlier studies suggest that preanalytical and methodological parameters impact analytical VEGF concentrations, but we have not found a comprehensive systematic review covering preanalytical procedures and methods for VEGF measurements.ObjectiveThis review aimed to evaluate the most critical factors during sample collection, sample handling, and the analytical methods that influence VEGF levels and therefore should be considered when planning a prospective collection of samples to get reproducible, comparable results.Material and methodsPubMed and Scopus databases were searched 2021/Nov/11. In addition, identification of records via other methods included reference, citation, and Google Scholar searches. Rayyan QCRI was used to handle duplicates and the selection process. Publications reporting preanalytical handling and/or methodological comparisons using human blood samples were included. Exclusion criteria were biological, environmental, genetic, or physiological factors affecting VEGF. The data extraction sheets included bias assessment using the QUADAS-2 tool, evaluating patient selection, index-test, reference standard, and flow and timing. Concentrations of VEGF and results from statistical comparisons of analytical methods and/or preanalytical sample handling and/or different sample systems were extracted. The publications covering preanalytical procedures were further categorized based on the stage of the preanalytical procedure. Meta-analysis was used to visualize VEGF concentrations among healthy individuals. The quality of evidence was rated according to GRADE.ResultsWe identified 1596 publications, and, after the screening process, 43 were considered eligible for this systematic review. The risk of bias estimation was difficult for 2/4 domains due to non-reported information. Four critical steps in the preanalytical process that impacted VEGF quantification were identified: blood drawing and the handling before, during, and after centrifugation. Sub-categorization of those elements resulted in nine findings, rated from moderate to very low evidence grade. The choice of sample system was the most reported factor. VEGF levels (mean [95% CI]) in serum (n = 906, 20 publications), (252.5 [213.1–291.9] pg/mL), were approximated to ninefold higher than in plasma (n = 1122, 23 publications), (27.8 [23.6–32.1] pg/mL), based on summarized VEGF levels with meta-analysis. Notably, most reported plasma levels were below the calibration range of the used method.ConclusionWhen measuring circulating VEGF levels, choice of sample system and sample handling are important factors to consider for ensuring high reproducibility and allowing study comparisons. Protocol: CRD42020192433

ДИФЕРЕНЦІАЛЬНА ДІАГНОСТИКА ЦЕРЕБРАЛЬНИХ СУДИННИХ ВАД І ОБ’ЄМНИХ НОВОУТВОРЕНЬ ФУНКЦІОНАЛЬНО ВАЖЛИВИХ ДІЛЯНОК МОЗКУ: КРИТЕРІЇ ВИБОРУ НЕЙРОХІРУРГІЧНОЇ ТАКТИКИ

Introduction. We believe, that in the planning of the surgical removal of cerebral vascular malformations (CVM) of eloquent brain areas, a question of whether they include the functionally sustainable brain tissue remains relevant. The question of whether the surgical procedure is safe is paramount. Aim. To assess the value of magnetic resonance (MR) tractography in deciding on the tactics of surgical treatment of CVM through comparison with morphological studies. Study methods. A review of the literature concerning the surgical treatment of cavernous malformations (CM) and arteriovenous malformations (AVM) localized in eloquent brain areas (EBA). Four patients with CVM of EBA were selected based on the availability of MR tractography data and histologic specimens. The method of optical microscopy was used to study microslides stained with the classic (hematoxylin-eosin) and specialized methods (Masson’s and Hart’s methods). Results. Patients’ MR-tractography data showed the presence of conductive paths in the tissues of CM and AVM and the reduced fractional anisotropy in the regions of interest, which indicates their involvement. During optical microscopy of specimens of CVMs, we found brain tissues between pathological vessels. To our opinion, this explains the visualization of conducting paths in CVMs during MR tractography. Conclusions. When planning surgeries in case of CVMs, attention should be paid to the results of conductive path visualization. According to MR tractography and morphological data, in some cases, there is brain parenchyma in the structure of CMs and AVMs, which may require additional attention in deciding on the radical resection of CVMs of EBAs.

Surgical Treatment of Cardiac Tumors Combined with Coronary Pathology

Introduction. Cardiac tumors (CT) occur in 0.3-0.7% of general population according to autopsies. The combination of CT with coronary artery disease (CAD) significantly complicates the clinical course of the disease.&#x0D; The aim. To study the frequency, features of the course and surgical treatment of patients with CT combined with CAD.&#x0D; Materials and methods. In the period from 01.01.1969 to 31.12.2020, surgical treatment of 976 patients with CT was performed at the National Amosov Institute of Cardiovascular Surgery of the NAMS of Ukraine, and 41 (4.2%) of these patients had lesions of the coronary arteries. In 39 patients (95.1%), CT were represented by benign tumors (myxomas), in 2 (2.4%) by malignant, poorly differentiated sarcoma and immature teratoma. For the correction of the pathology of coronary vessels, a whole range of surgical methods was used: stenting of left anterior descending artery (LAD), which was performed immediately before surgery to remove CT, in 3 patients (7.3%); coronary artery bypass grafting in 35 patients (85.4%); in cases of the presence of a muscular bridge that narrowed the LAD, dissection of this structure was performed in 2 patients (4.9%); left ventricular aneurysm repair surgery in 1 patient (2.4%). In 7 patients (17.1%), the operation was performed on urgent indications.&#x0D; Results. The average number of grafted arteries was 1.9 ± 0.3 (1 to 4) per patient. There were no mortality. Of the 41 patients with coronary artery lesions with CT, there were 2 cases of acute CAD as a result of their embolism by tumor fragments. Clinical manifestations in these patients differed significantly.&#x0D; Conclusions. Occurrence of coronary artery embolism in patients with CT according to our data is 0.2% of all patients with CT. CAD accompanies tumor lesions in 4.1% of cases and is diagnosed by angiography and computed tomography. To correct the lesion of the coronary arteries in CT, the full range of surgical techniques is used, including stenting of the coronary artery (spacecraft), coronary artery bypass grafting, removal of the myocardial bridge.

Acute occurrence and rupture of a dissecting basilar artery aneurysm in a patient with SARS-CoV-2

The article describes a clinical case of a dissecting basilar artery aneurysm in a patient with SARS-CoV-2. The patient was treated in the infectious diseases hospital for bilateral polysegmental pneumonia on the background of COVID-19. Suddenly, a focal neurological deficit occurred and grew in dynamics in the form of abducens nerve paresis, bulbar disorders, and right-sided hemiparesis. MSCT and MSCT-angiography were performed in dynamics. During the first examination, the pathology of the cerebral vessels was not revealed, but 10 days later, there was detected a fusiform aneurysm of the basilar artery with a diverticulum, the rupture of which led to massive hemorrhage and an unfavorable treatment outcome. The patient's primary symptomatology could be due to impaired blood flow in the perforating branches in the area of the started dissection of the basilar artery.

Hydroquinone predisposes for retinal pigment epithelial (RPE) cell degeneration in inflammatory conditions

In addition to hypoxia, inflammation is capable of inducing vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells. Excessive levels of VEGF promote choroidal neovascularization and thereby contribute to the pathogenesis of wet age-related macular degeneration (AMD). Intravitreal anti-VEGF injections ameliorate pathological vessel neoformation in wet AMD but excessive dampening of VEGF can result in a degeneration of the RPE. In the present study, we induced VEGF production by exposing human ARPE-19 cells to the pro-inflammatory IL-1α and subsequently to hydroquinone, a component of tobacco smoke that is a major environmental risk factor for AMD. Effects were monitored by measuring the levels of VEGF and anti-angiogenic pigment epithelium-derived factor (PEDF) using an enzyme-linked immunosorbent assay (ELISA) technique. In addition, we measured the production of reactive oxygen species (ROS) using the 2′,7′-dichlorofluorescin diacetate (H2DCFDA) probe and studied the effects of two anti-oxidants, ammonium pyrrolidinedithiocarbamate (APDC) and N-acetyl-cysteine (NAC), on VEGF production. Cellular and secreted VEGF as well as secreted PEDF levels were reduced at all tested hydroquinone concentrations (10, 50, or 200 µM); these effects were evident prior to any reduction of cell viability evoked by hydroquinone. Cell viability was carefully explored in our previous study and verified by microscoping in the present study. APDC further reduced the VEGF levels, whereas NAC increased them. The 50 μM concentration of hydroquinone increased ROS production in ARPE-19 cells primed with IL-1α. Hydroquinone disturbs the regulatory balance of VEGF and PEDF in inflammatory conditions. These data support the idea that hydroquinone mediates RPE degeneration by reducing VEGF levels and may predispose to dry AMD since VEGF is as well important for retinal integrity.

Loss of the heterogeneous expression of flippase ATP11B leads to cerebral small vessel disease in a normotensive rat model

Cerebral small vessel disease (SVD) is the leading cause of vascular dementia, causes a quarter of strokes, and worsens stroke outcomes. The disease is characterised by patchy cerebral small vessel and white matter pathology, but the underlying mechanisms are poorly understood. This microvascular and tissue damage has been classically considered secondary to extrinsic factors, such as hypertension, but this fails to explain the patchy nature of the disease, the link to endothelial cell (EC) dysfunction even when hypertension is absent, and the increasing evidence of high heritability to SVD-related brain damage. We have previously shown the link between deletion of the phospholipase flippase Atp11b and EC dysfunction in an inbred hypertensive rat model with SVD-like pathology and a single nucleotide polymorphism (SNP) in ATP11B associated with human sporadic SVD. Here, we generated a novel normotensive transgenic rat model, where Atp11b is deleted, and show pathological, imaging and behavioural changes typical of those in human SVD, but that occur without hypertension. Atp11bKO rat brain and retinal small vessels show ECs with molecular and morphological changes of dysfunction, with myelin disruption in a patchy pattern around some but not all brain small vessels, similar to the human brain. We show that ATP11B/ATP11B is heterogeneously expressed in ECs in normal rat and human brain even in the same transverse section of the same blood vessel, suggesting variable effects of the loss of ATP11B on each vessel and an explanation for the patchy nature of the disease. This work highlights a link between inherent EC dysfunction and vulnerability to SVD white matter damage with a marked heterogeneity of ECs in vivo which modulates this response, occurring even in the absence of hypertension. These findings refocus our strategies for therapeutics away from antihypertensive (and vascular risk factor) control alone and towards ECs in the effort to provide alternative targets to prevent a major cause of stroke and dementia.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

Cerebrospinal Fluid Biomarkers for Cerebral Amyloid Angiopathy Diagnosis.

An accurate diagnosis of sporadic cerebral amyloid angiopathy (CAA) is critical for patient management and research (including clinical trials) for this common small vessel pathology of the brain. While the "big bang" of the CAA field has been the device and wide adoption of the clinico-radiological Boston criteria which allowed for CAA diagnosis during life, these criteria are not without major shortcoming. As it is now becoming evident that CAA is probably not a single disease, but rather represents divergent pathophysiological phenotypes and clinical trajectories, new biomarker-driven diagnostic approaches should be sought. One such complimentary approach for CAA diagnosis is the use of cerebrospinal fluid biomarkers (CSF), which could provide dynamic measures of the underlying disease process and is discussed in this commentary given exciting new advances. A hint on how the practicing clinician could apply the current CSF data for CAA diagnosis is also provided.

Abstract 488: Glutathione-CaSR Interaction Contributes To Glutathione Regulation Of Angiogenesis

Introduction: In addition to its classic role in redox chemistry, glutathione (GSH) also acts as an allosteric regulator of the calcium-sensing receptor (CaSR). CaSR has been found in a variety of cell types including endothelial cells (ECs), where its activity has been linked to EC adhesion and migration. Although a relationship between GSH and CaSR has been discovered, no link has been established between GSH-CaSR interaction and regulation of angiogenesis. We hypothesize a novel mechanism for GSH regulation of blood vessel development occurs through an extracellular interaction with CaSR as a part of physiological and pathological angiogenesis. Methods: Matrigel tube formation and wound healing assays were used to measure EC activity. RGECO1.2 was used to measure changes in intracellular calcium. Cell surface expression assay was used to measure surface CaSR expression. Cell counts and flow cytometry were used to monitor cell proliferation and cell cycle progression. Endothelial and mesenchymal markers were measured using real-time PCR. Results: Extracellular GSH increased endothelial tube length and branching in tube formation assay, while a selective CaSR inhibitor abrogated these effects. GSH also influenced EC migration as measured by wound healing assay. GSH or a CaSR agonist (R-568) reduced surface CaSR expression, with no changes in intracellular calcium. Extracellular GSH alters EC proliferation and cell cycle progression, coinciding with alterations in endothelial phenotype along the endothelial-mesenchymal spectrum. Conclusion: In addition to its classic antioxidant role, GSH appears to act extracellularly to influence EC activity. GSH caused significant increases in EC branching as measured by tube formation assay. The use of a selective CaSR inhibitor confirms the contribution of CaSR to this effect. Additionally, GSH influenced EC migration in wound healing assays. These results could be explained by GSH-CaSR-mediated alterations in endothelial differentiation. These results suggest a role for GSH in vascular development and angiogenesis, through a ligand interaction with the CaSR G-protein coupled receptor, representing a novel mechanism of action for physiological and pathological blood vessel development.

Investigating a Ligand‐receptor Role for Glutathione in Angiogenesis

IntroductionIn addition to its classic role in redox chemistry, glutathione (GSH) also acts as an allosteric regulator of the calcium‐sensing receptor (CaSR). CaSR expression has been found in a variety of cell types including vascular smooth muscle and endothelial cells (ECs), where its activity has been linked to EC adhesion and migration. Although a relationship between GSH and CaSR has been discovered, no link has been established between GSH‐CaSR interaction and regulation of blood vessel development. We hypothesize that a novel mechanism for GSH regulation of blood vessel development occurs through an extracellular interaction with CaSR as a part of normal physiology, with potential extensions to pathological angiogenesis.MethodsMatrigel tube formation and under agarose migration assays were used to measure EC activity in primary human aortic endothelial cells (HAECs). Fura‐2 AM was used with cells from an hTERT immortalized aortic endothelial cell line (tHAECs) to measure changes in intracellular calcium. Cell surface expression assay (CelLISA) and flow cytometry were used to measure surface CaSR expression. Endothelial and endothelial‐mesenchymal transition (EndoMT) markers were measured using real‐time PCR.ResultsExtracellular application of GSH increased endothelial tube length and branching in tube formation assay, while treating cells with selective CaSR inhibitor (NPS‐2143) abrogated these effects, indicating a role for CaSR in vascular modeling. Extracellular GSH influenced EC migration as measured by under agarose migration assay. GSH or a CaSR agonist (R‐568) reduced surface CaSR expression, with little/no change in intracellular calcium. RT‐PCR results suggest that extracellular GSH alters endothelial phenotype along the endothelial‐mesenchymal spectrum, promoting endothelial differentiation.ConclusionIn addition to its classic antioxidant role, GSH appears to act extracellularly to influence EC activity. GSH caused significant increases in EC branching as measured by the tube formation assay. With the use of a selective CaSR inhibitor, we were able to confirm the contribution of CaSR to this effect. Additionally, GSH influenced EC migration in the under agarose assay. These results could be explained by GSH‐CaSR‐mediated alterations in endothelial differentiation. These results suggest a role for GSH in vascular development and angiogenesis, through a ligand interaction with the CaSR G‐protein coupled receptor, which represents a novel mechanism of action for physiological and pathological blood vessel development.

An autopsy case of TAFRO syndrome with multiple cerebral infarctions caused by small vessel pathology.

An autopsy case of TAFRO syndrome with multiple cerebral infarctions caused by small vessel pathology.

Measurement of Blood Velocity With Laser Scanning Microscopy: Modeling and Comparison of Line-Scan Image-Processing Algorithms.

Laser scanning microscopy is widely used to measure blood hemodynamics with line-scans in physiological and pathological vessels. With scans of broken lines, i.e., lines made of several segments with different orientations, it also allows simultaneous monitoring of vessel diameter dynamics or the activity of specific cells. Analysis of red blood cell (RBC) velocity from line-scans requires specific image-processing algorithms, as angle measurements, Line-Scanning Particle Image Velocimetry (LSPIV) or Fourier transformation of line-scan images. The conditions under which these image-processing algorithms give accurate measurements have not been fully characterized although the accuracy of measurements vary according to specific experimental parameters: the vessel type, the RBC velocity, the scanning parameters, and the image signal to noise ratio. Here, we developed mathematical models for the three previously mentioned line-scan image-processing algorithms. Our models predict the experimental conditions in which RBC velocity measurements are accurate. We illustrate the case of different vessel types and give the parameter space available for each of them. Last, we developed a software generating artificial line-scan images and used it to validate our models.

Visceral and renal malperfusion syndromes in acute aortic dissection type A: the fate of the branch vessel.

Malperfusion in acute aortic dissection is not uncommonly observed and associated with a highly significant increase in mortality and morbidity. Of the various malperfusion syndromes, visceral and renal involvement is the most challenging in terms of correct and timely diagnosis as well as the choice of management strategy. The aim of this study was to identify the pathology and associated fate of each visceral and renal vessel in acute type A dissections. Over a 12-year period, 167 consecutive patients with acute dissection type A extending into the thoracoabdominal aorta were included and radiographic images analyzed with a focus on individual branch vessel pathology and dependent organ perfusion. Sixty-five patients (39%) were diagnosed with radiological signs of malperfusion on the CT Images. Of those, 20% expired during the hospital stay, compared to 8% without malperfusion. The left renal artery was the most frequently affected by dissection (31%) or false lumen supply (28%). False lumen perfusion was more often associated with manifest malperfusion than an extension of the dissection flap into the branch vessel. During the study period, there was no preference of surgical procedure treating the malperfusion. Malperfusion of the visceral/renal branches of a dissected aorta represents a manifest indicator for postoperative mortality and morbidity. Neither clinical outcome, nor the fate of individual vessels can reliably be predicted prior to proximal reconstruction and thus, surgical strategy cannot generally be defined alone by radiological findings.