Vessel Wall Structure Research Articles

Immunocellular microenvironment of the vascular wall of cerebral aneurysms: What is the role of inflammatory cells in aneurysmal remodeling?

AbstractIntracranial aneurysms (IAs) may afflict up to 5% of the general population, or up to 15 million individuals in the US. The two forms of IAs that can be recognized by their shape are saccular and nonsaccular IAs, with uncommon aneurysm types, fusiform and dissecting aneurysms, comprising 13% of nonsaccular IAs. Conceivably, among the various risk factors for IA development, vessel wall inflammation represents a major cause. Accordingly, IAs may not necessarily be the result of passive widening of vessel wall structures, but may also be the result of inflammation and tissue degeneration. Thus, flow‐induced vascular remodeling during IA pathogenesis may reflect immune cell infiltration and consequent release of proinflammatory cytokine, chemokine, and matrix metalloproteinase that contribute to vessel wall degeneration and weakening. Thus, infiltrating neutrophils, macrophages, T‐lymphocytes and complement factors, and the resulting immune microenvironment may be pertinent in IA pathogenesis.

Prevalence of intracerebral thrombus detected by optical coherence tomography in patients with posterior circulation stroke or transient ischemic attack

BackgroundThe incidence of thrombosis in patients with intracranial atherosclerotic stenosis (ICAS) remains unclear. Optical coherence tomography (OCT) has the potential to explore the vessel wall structure of posterior-circulation ICAS because...

CT Imaging Findings of Pulmonary Artery Stenosis: A Pictorial Review.

Pulmonary artery stenosis represents a group of disorders involving main, branch or peripheral pulmonary arteries with pain, dyspnea, hemoptysis or even no symptoms. Early diagnosis and timely intervention are crucial for reducing mortality, but timely diagnosis is challenging due to the non-specific symptoms. Computed tomography pulmonary angiography (CTPA) is useful in the diagnosis because it can provide more details about abnormal changes in the lumen, vessel wall and adjacent mediastinal structures. Congenital and acquired pulmonary artery anomalies have some characteristics on CTPA, which can be useful for differential diagnosis. Awareness of these conditions is important for radiologists. This pictorial review provides an overview of CTPA imaging features of pulmonary artery stenosis.

Shared genetic etiology of vessel diseases: A genome-wide multi-traits association analysis

BackgroundThe comorbidity among vascular diseases has been widely reported, however, the contribution of shared genetic components remains ambiguous. MethodsBased on genome-wide association study summary statistics, we employed statistical genetics methodologies to explore the shared genetic basis of eight vascular diseases: coronary artery disease, abdominal aortic aneurysm, ischemic stroke, peripheral artery disease, thoracic aortic aneurysm, phlebitis, varicose veins, and venous thromboembolism. We assessed global and local genetic correlations among these disorders by linkage disequilibrium score regression, high-definition likelihood, and local analysis of variant association. Cross-trait analyses conducted with CPASSOC identified pleiotropic variants and loci. Further, biological pathways at the multi-omics level were explored using multimarker analysis of genomic annotation, transcriptome-wide and proteome-wide association studies. Causal associations among the vascular diseases were evaluated by mendelian randomization and latent causal variable to assess vertical pleiotropic effects. ResultsWe found significant global genetic associations in 18 pairs of vascular diseases. Additionally, we discovered 317 unique genomic regions where at least one pair of traits demonstrated significant correlation. Multi-trait association analysis identified 19,361 significant potential pleiotropic variants in 274 independent pleiotropic loci. Multi-trait colocalization analysis revealed 56 colocalized loci in specific disease sets. Gene-based analysis identified 700 potential pleiotropic genes, which were subsequently validated at both transcriptome and protein levels. Gene-set enrichment analysis supports the role of biological pathways such as vessel wall structure, coagulation and lipid transport in vascular disease. Additionally, 7 pairs of vascular diseases have a causal relationship. ConclusionsOur study indicates a shared genetic basis and the presence of common risk genes among vascular diseases. These findings offer novel insights into potential mechanisms underlying the association between vascular diseases, as well as provide guidance for interventions and treatments of multi-vascular conditions.

Modeling of rabbit femoral artery occlusion by high-intensity focused ultrasound

One of the effective methods of artery and vein occlusion used in experimental studies and in clinical practice for certain diseases is local exposure of vessels to high-intensity focused ultrasound (HIFU). The wide use of this method in our country is limited by the lack of appropriate domestic equipment. At the Peter the Great St. Petersburg Polytechnic University, in the Laboratory of Ultrasound Technologies of the Center for Advanced Research, a stand for HIFU effects on various biological objects has been developed. There is no experience in using this device in angiology yet. The purpose of our research was to study the possibility of using Medusa 008, a high-tech mobile medical device designed for ultrasound diagnosis and personalized HIFU therapy, to model vascular occlusion and stop blood flow during irradiation. Materials and methods. The object of the study is the femoral artery of a rabbit. The source of HIFU is Medusa 008, the high-tech mobile medical device designed for ultrasound diagnostics and personalized HIFU-therapy with radiation frequency of 2 MHz (prototype). The following irradiation modes were used in the research: irradiation duration - 50 ms, pause between exposures – 10 ms, number of pulses – 20, 30, 40. The following energy values corresponded to these modes: 58 J, 87 J, 116 J. Irradiation of the femoral artery of an anesthetized rabbit was performed percutaneously. We used ultrasound to visualize the arteries and measure the blood flow velocity. According to ultrasound data, after HIFU irradiation, blood flow in the artery stopped. The factor contributing to arterial occlusion is the cessation of blood flow during irradiation. A histological examination of the area of the irradiated artery revealed structural changes in all layers of the vascular wall. Results. HIFU irradiation with intensity of 87 and 116 J has a significant dose-dependent destructive effect on the muscular arterial wall. The more intense damaging irradiation (116 J) causes smooth muscle cell necrosis. The time of direct influence on the vessel wall structures did not exceed 3 sec. During the experiment, we found that HIFU in the used modes causes temperature increase up to 45–60 оC, which is enough for thermal damage of cells in the irradiation zone. Conclusion. Thus, as a result of the above experiments, it was shown that Medusa 008, the high-tech mobile medical device designed for ultrasound diagnostics and personalized HIFU-therapy can be used to simulate vascular occlusion.

Improved stent sharpness evaluation with super-resolution deep learning reconstruction in coronary CT angiography.

This study aimed to assess the impact of super-resolution deep learning reconstruction (SR-DLR) on coronary CT angiography (CCTA) image quality and blooming artifacts from coronary artery stents in comparison to conventional methods, including hybrid iterative reconstruction (HIR) and deep learning-based reconstruction (DLR). A retrospective analysis included 66 CCTA patients from July to November 2022. Major coronary arteries were evaluated for image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). Stent sharpness was quantified using 10%-90% edge rise slope (ERS) and 10%-90% edge rise distance (ERD). Qualitative analysis employed a 5-point scoring system to assess overall image quality, image noise, vessel wall, and stent structure. SR-DLR demonstrated significantly lower image noise compared to HIR and DLR. SNR and CNR were notably higher in SR-DLR. Stent ERS was significantly improved in SR-DLR, with mean ERD values of 0.70 ± 0.20 mm for SR-DLR, 1.13 ± 0.28 mm for HIR, and 0.85 ± 0.26 mm for DLR. Qualitatively, SR-DLR scored higher in all categories. SR-DLR produces images with lower image noise, leading to improved overall image quality, compared with HIR and DLR. SR-DLR is a valuable image reconstruction algorithm for enhancing the spatial resolution and sharpness of coronary artery stents without being constrained by hardware limitations. The overall image quality was significantly higher in SR-DLR, resulting in sharper coronary artery stents compared to HIR and DLR.

Spatiotemporal analysis of the effects of exercise on the hemodynamics of the aorta in hypertensive rats using fluid-structure interaction simulation

Abstract Background and Objective Hemodynamic changes that lead to increased blood pressure represent the main drivers of organ damage in hypertension. Prolonged increases to blood pressure can lead to vascular remodeling, which also affects vascular hemodynamics during the pathogenesis of hypertension. Exercise is beneficial for relieving hypertension, however the mechanistic link between exercise training and how it influences hemodynamics in the context of hypertension is not well understood. Methods n exercise model was developed using spontaneously hypertensive rats (SHR) subject to a 12-week treadmill training regime. The heart rates and blood pressures of rats were measured using the tail cuff method, while micro-computed tomography (CT) scanning was used to develop three-dimensional structures of rat aorta, and ultrasound was used to detect rat aortic blood flow and changes to vessel wall structures. Computational fluid dynamics (CFD) and fluid-structure interaction (FSI) models were used to simulate and measure hemodynamic parameters of the rat aortic vessels. In parallel, Masson staining was performed on fixed samples of blood vessels to investigate collagen volume fraction. Hypertensive rats in the sedentary and long-term exercise training groups were subjected to a single bout exercise training, and their aortic hemodynamic parameters were analyzed before, 5 min, 24 h, and 72 h after the single bout exercise. Results Of the two models, in comparison to actual ultrasonic measurement values recorded, we found that numerical simulation results from the FSI model could more accurately model blood flow in the ascending aorta of hypertensive rats, compared to the CFD model. Moreover, longterm exercise training improved local hemodynamic parameters of blood vessels, and led to improvements in adverse hemodynamic features documented, including time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). Longterm exercise training of SHR also improved local vascular collagen deposition in the aorta, while improvements in vascular remodeling were also correlated with favorable hemodynamic parameters. Compared with sedentary SHR, signals for low TAWSS regions of the aortic arch in SHR on the long-term exercise regime shifted to the position of the ascending aorta after a single bout of exercise. Conclusions This study demonstrates that FSI is informative to study the spatiotemporal effects of long-term exercise training on hemodynamic changes within the aortas of hypertensive rats, and that long-term exercise is beneficial through its effects to modulate vascular hemodynamics in hypertension.

Microvascular damage, neuroinflammation and extracellular matrix remodeling in Col18a1 knockout mice as a model for early cerebral small vessel disease

Collagen type XVIII (COL18) is an abundant heparan sulfate proteoglycan in vascular basement membranes. Here, we asked (i) if the loss of COL18 would result in blood-brain barrier (BBB) breakdown, pathological alterations of small arteries and capillaries and neuroinflammation as found in cerebral small vessel disease (CSVD) and (ii) if such changes may be associated with remodeling of synapses and neural extracellular matrix (ECM). We found that 5-month-old Col18a1−/− mice had elevated BBB permeability for mouse IgG in the deep gray matter, and intravascular erythrocyte accumulations were observed brain-wide in capillaries and arterioles. BBB permeability increased with age and affected cortical regions and the hippocampus in 12-month-old Col18a1−/− mice. None of the Col18a1−/− mice displayed hallmarks of advanced CSVD, such as hemorrhages, and did not show perivascular space enlargement. Col18a1 deficiency-induced BBB leakage was accompanied by activation of microglia and astrocytes, a loss of aggrecan in the ECM of perineuronal nets associated with fast-spiking inhibitory interneurons and accumulation of the perisynaptic ECM proteoglycan brevican and the microglial complement protein C1q at excitatory synapses. As the pathway underlying these regulations, we found increased signaling through the TGF-ß1/Smad3/TIMP-3 cascade. We verified the pivotal role of COL18 for small vessel wall structure in CSVD by demonstrating the protein's involvement in vascular remodeling in autopsy brains from patients with cerebral hypertensive arteriopathy. Our study highlights an association between the alterations of perivascular ECM, extracellular proteolysis, and perineuronal/perisynaptic ECM, as a possible substrate of synaptic and cognitive alterations in CSVD.

The biomechanical effects of different membrane layer structures and material constitutive modeling on patient-specific cerebral aneurysms.

The prevention, control and treatment of cerebral aneurysm (CA) has become a common concern of human society, and by simulating the biomechanical environment of CA using finite element analysis (FEA), the risk of aneurysm rupture can be predicted and evaluated. The target models of the current study are mainly idealized single-layer linear elastic cerebral aneurysm models, which do not take into account the effects of the vessel wall structure, material constitution, and structure of the real CA model on the mechanical parameters. This study proposes a reconstruction method for patient-specific trilaminar CA structural modeling. Using two-way fluid-structure interaction (FSI), we comparatively analyzed the effects of the differences between linear and hyperelastic materials and three-layer and single-layer membrane structures on various hemodynamic parameters of the CA model. It was found that the numerical effects of the different CA membrane structures and material constitution on the stresses and wall deformations were obvious, but does not affect the change in its distribution pattern and had little effect on the blood flow patterns. For the same material constitution, the stress of the three-layer membrane structure were more than 10.1% larger than that of the single-layer membrane structure. For the same membrane structure, the stress of the hyperelastic material were more than 5.4% larger than that of the linear elastic material, and the displacement of the hyperelastic material is smaller than that of the linear elastic material by about 20%. And the maximum value of stress occurred in the media, and the maximum displacement occurred in the intima. In addition, the upper region of the tumor is the maximum rupture risk region for CA, and the neck of the tumor and the bifurcation of the artery are also the sub-rupture risk regions to focus on. This study can provide data support for the selection of model materials for CA simulation and analysis, as well as a theoretical basis for clinical studies and subsequent research methods.

Application and reduction of a nonlinear hyperelastic wall model capturing ex vivo relationships between fluid pressure, area, and wall thickness in normal and hypertensive murine left pulmonary arteries.

Pulmonary hypertension is a cardiovascular disorder manifested by elevated mean arterial blood pressure (>20 mmHg) together with vessel wall stiffening and thickening due to alterations in collagen, elastin, and smooth muscle cells. Hypoxia-induced (type 3) pulmonary hypertension can be studied in animals exposed to a low oxygen environment for prolonged time periods leading to biomechanical alterations in vessel wall structure. This study introduces a novel approach to formulating a reduced order nonlinear elastic structural wall model for a large pulmonary artery. The model relating blood pressure and area is calibrated using ex vivo measurements of vessel diameter and wall thickness changes, under controlled pressure conditions, in left pulmonary arteries isolated from control and hypertensive mice. A two-layer, hyperelastic, and anisotropic model incorporating residual stresses is formulated using the Holzapfel-Gasser-Ogden model. Complex relations predicting vessel area and wall thickness with increasing blood pressure are derived and calibrated using the data. Sensitivity analysis, parameter estimation, subset selection, and physical plausibility arguments are used to systematically reduce the 16-parameter model to one in which a much smaller subset of identifiable parameters is estimated via solution of an inverse problem. Our final reduced one layer model includes a single set of three elastic moduli. Estimated ranges of these parameters demonstrate that nonlinear stiffening is dominated by elastin in the control animals and by collagen in the hypertensive animals. The pressure-area relation developed in this novel manner has potential impact on one-dimensional fluids network models of vessel wall remodeling in the presence of cardiovascular disease.

Hypertension-associated changes in retinal blood vessel walls measured in vivo with polarization-sensitive optical coherence tomography

Blood vessel walls are made of organized fibrous tissue with intrinsic birefringence. Even in its very early stages, hypertension can change the structure of a blood vessel wall. In this paper, we demonstrated that this structural change associated with hypertension can be quantitatively measured non-invasively in the human retina using polarization-sensitive optical coherence tomography (PS-OCT). Measurements were performed with a relatively low-cost PS-OCT instrument in less than a minute per eye. Organizational loss in vessel wall tissue was quantified in hypertensive patients and compared to data obtained from age-matched healthy subjects. Our PS-OCT measurements showed that the vessel wall tissue in patients with hypertension is thicker, and exhibited lower birefringence, presumably due to a loss of tissue organization. The blood vessel wall birefringence index (BBI) is a newly introduced metric that combines vessel wall birefringence (decreases with hypertension) and thickness (increases with hypertension) into a single numerical value. Its purpose is to easily differentiate between the blood vessel walls of hypertensives and those of healthy subjects. Accurately determining the thickness of the blood vessel wall relies on access to polarization-sensitive data: a linear increase in retardation in the vessel wall with depth and stable retardation values below the vessel wall to determine the lower edge of the vessel wall. Based on receiver operating characteristic (ROC) curves, BBI showed 99 % sensitivity and 100 % specificity when discriminating normotensive (N = 11) and hypertensive (N = 11) subjects.

Non-Invasive Retinal Blood Vessel Wall Measurements with Polarization-Sensitive Optical Coherence Tomography for Diabetes Assessment: A Quantitative Study.

Diabetes affects the structure of the blood vessel walls. Since the blood vessel walls are made of birefringent organized tissue, any change or damage to this organization can be evaluated using polarization-sensitive optical coherence tomography (PS-OCT). In this paper, we used PS-OCT along with the blood vessel wall birefringence index (BBI = thickness/birefringence2) to non-invasively assess the structural integrity of the human retinal blood vessel walls in patients with diabetes and compared the results to those of healthy subjects. PS-OCT measurements revealed that blood vessel walls of diabetic patients exhibit a much higher birefringence while having the same wall thickness and therefore lower BBI values. Applying BBI to diagnose diabetes demonstrated high accuracy (93%), sensitivity (93%) and specificity (93%). PS-OCT measurements can quantify small changes in the polarization properties of retinal vessel walls associated with diabetes, which provides researchers with a new imaging tool to determine the effects of exercise, medication, and alternative diets on the development of diabetes.

Effects of different preservation schemes on isolated rat artery.

Allogeneic blood vessels are regarded as one of the best natural substitutes for diseased blood vessels due to their good vascular compliance and histocompatibility. Since the supply and demand of allograft blood vessels do not always match in time and space, a good preservation scheme for isolated blood vessels is essential. The abdominal aortas of 110 male Sprague-Dawley (SD) rats were randomly divided into three groups, including cold storage group (4°C) (CSG), frozen storage group (FSG) and ambient storage group (25 ± 2°C) (ASG). Seven time points of preservation for 1, 3, 5, 7, 14, 30 and 90 days were set for detection. The changes in vascular physiological function were evaluated by MTT test and vasoconstriction ability detection, and the changes in vascular wall structure were evaluated by the tension tolerance test and pathological staining. The vascular function of CSG was better than FSG within first the 7 days, but the result was opposite since the 14th day. The vascular wall structure, collagen and elastic fibres of vessels, in CSG, showed oedema within 30 days, and continuous disintegration and rupture at 90 days. The vessel wall structure of FSG remained intact within 90 days. The tensile strength of the vessels in CSG was better than that in FSG within 5 days, and there was no statistical difference between the two groups between the 7th and 30th day, and then, the FSG was higher than CSG on the 90th day. Both cold storage and frozen storage could be applied as safe and effective preservation schemes for isolated rat artery within first 30 days. Cold storage is recommended when the storage time is <14 days, and then, frozen storage is better.

The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action.

Non-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker.

Correlation between stem cell molecular phenotype and atherosclerotic plaque neointima formation and analysis of stem cell signal pathways.

Vascular stem cells exist in the three-layer structure of blood vessel walls and play an indispensable role in angiogenesis under physiological conditions and vascular remodeling under pathological conditions. Vascular stem cells are mostly quiescent, but can be activated in response to injury and participate in endothelial repair and neointima formation. Extensive studies have demonstrated the differentiation potential of stem/progenitor cells to repair endothelium and participate in neointima formation during vascular remodeling. The stem cell population has markers on the surface of the cells that can be used to identify this cell population. The main positive markers include Stem cell antigen-1 (Sca1), Sry-box transcription factor 10 (SOX10). Stromal cell antigen 1 (Stro-1) and Stem cell growth factor receptor kit (c-kit) are still controversial. Different parts of the vessel have different stem cell populations and multiple markers. In this review, we trace the role of vascular stem/progenitor cells in the progression of atherosclerosis and neointima formation, focusing on the expression of stem cell molecular markers that occur during neointima formation and vascular repair, as well as the molecular phenotypic changes that occur during differentiation of different stem cell types. To explore the correlation between stem cell molecular markers and atherosclerotic diseases and neointima formation, summarize the differential changes of molecular phenotype during the differentiation of stem cells into smooth muscle cells and endothelial cells, and further analyze the signaling pathways and molecular mechanisms of stem cells expressing different positive markers participating in intima formation and vascular repair. Summarizing the limitations of stem cells in the prevention and treatment of atherosclerotic diseases and the pressing issues that need to be addressed, we provide a feasible scheme for studying the signaling pathways of vascular stem cells involved in vascular diseases.

Forms of cell death and targets at photodynamic therapy

The aim of the study is to study the results of the most significant studies on the forms of tumor cell death and targets in photodynamic therapy (PDT). Material and methods. On the problem, we analyzed the Scopus, WoS, MedLine databases and found 31 sources. Results. PDT is an important tool for studying the pathways leading to the complete devitalization of a malignant tumor. Moreover, subcellular targets in pdt are determined by the properties of photosensitizers (PS). Particularly effective targets are lysosomes and mitochondria, including those for class I PS, photofrin. This explains the effectiveness of photofrin, although it has a weak absorption band in the region of 630 nm with a limited penetration depth into tissues. The development of new PSs with subcellular targets of photofrin, but with an absorption band in the long-wavelength region, is becoming very topical. Such FS are ideal for PDT. Second-generation PSS have already been introduced into clinical practice. The effectiveness of PDT with the use of photoditazine was shown. The mechanisms of action and targets of this PS have been established. The latter include the vessel wall, cytoplasmic membranes, and internal structures of tumor cells. The main type of neoplastic cell death during PDT with photoditazine is direct photocoagulation and ischemic necrosis of the tumor parenchyma due to the destruction of the neoplasm vascular bed. Today, considerable attention is paid to the development of other new PSS, namely, bacteriochlorophyll-α derivatives, which have an intense absorption of radiation in the long-wavelength region of the spectral range. These include the disulfide-bpi conjugate, which contains 2 molecules of dipropoxybacteriopurpurinimide and a cystamine residue, the results of which showed its high efficiency due to the destruction of the tumor vascular bed, the rapid slowdown and/or cessation of cell proliferative activity and their death by necrosis and apoptosis. Rapid progress in studying the mechanisms of action of PDt has shown that autophagy triggering using the lysosomal compartment to degrade and utilize damaged cell organelles and paraptosis associated with defective proteins in the endoplasmic reticulum also play an important role in the elimination of tumor cells. Conclusion. Apoptosis, autophagy, and paraptosis can occur after photodamage to mitochondria, lysosomes, or the endoplasmic reticulum. The balance of cell death pathways is often a determining factor in the effectiveness of PDT.

Lack of PI 3-kinase isoform p110alpha impairs SMC differentiation and proliferation and promotes aortic aneurysm formation

Abstract Background Proliferation and phenotypic modulation of vascular smooth muscle cells (SMCs) significantly contribute to the functionality of the aortic wall. Dysregulation of underlying signal transduction pathways impairs the vessel wall structure and promote the development and progression of abdominal aortic aneurysms (AAA). The PI 3-kinase (PI3K) isoform p110α is activated downstream of receptor tyrosine kinases (RTKs) and represents the most relevant PI3K isoform in SMCs. Aim This project follows the hypothesis that p110α deficiency impairs proliferation and phenotypic modulation of SMCs as well as the structure of the extracellular matrix (ECM) and therefore promotes the development and progression of AAA. It was investigated how p110α deficiency affects the plasticity of SMCs, the production and structure of ECM components, and the formation of AAA. Methods and results Western blot analyses showed that SMCs isolated from smooth muscle specific p110α−/− (sm-p110α−/−) mice were characterized by decreased expression of the differentiation markers sm-α-actin, calponin and sm-MHC. Mechanistically, phosphorylation of key modulators of the SMC phenotype – AKT1, AKT2, FOXO1, -3 and -4 as well as GSK3β – was impaired in p110α−/− SMCs after RTK stimulation. These findings indicate that phenotypic modulation of p110α−/− SMCs is restricted. In addition, protein expression of elastin and fibrillin was reduced in p110α−/− SMCs. In silico analysis (MatLab macro CT-FIRE and Curvalign) of the ECM produced by SMCs in vitro revealed a significantly reduced elastin fiber length and width in p110α−/− SMCs compared to fibers produced by WT SMCs (p&amp;lt;0.05). Consistently, aortas from sm-p110α−/− mice showed a significantly higher number of elastic fiber breaks specifically in the thoracic section than WT controls (289±31 mmm–2 versus 190±9 mmm–2, n=5, p=0.015). Aortic aneurysms in sm-p110α−/− mice and wild-type littermates were analyzed using the established porcine pancreatic elastase (PPE) model. PPE was perfused into the infrarenal aorta to induce AAA formation. Ultrasound examination of the aorta revealed an enlarged aortic diameter in all PPE-treated mice. However, the increase in aortic diameter in sm-p110α−/− mice (70.16±10.82% mm, n=9) was significant more pronounced compared to wild-type animals (42.44±5.99%, n=10) (p&amp;lt;0.05). Three days after PPE perfusion, the number of elastic fiber breaks was significantly increased, and amount of proliferating SMCs were decreased in the infrarenal aorta of sm-p110α−/− mice compared to WT controls. Conclusion p110α deficiency in SMCs impairs aortic wall structure and promotes the development and progression of aortic aneurysms. Mechanistically, p110α activity maintains a differentiated SMC phenotype as well as the expression and assembly of ECM components. These data identify p110α signaling as a modifiable target for preventive and therapeutic strategies for aortic aneurysms. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Deutsche Forschungsgemeinschaft

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.

Imaging features of adult moyamoya disease patients with anterior intracerebral hemorrhage based on high-resolution magnetic resonance imaging

This study aimed to identify the high-resolution magnetic resonance imaging (HRMRI) features of moyamoya disease (MMD) patients with anterior intracerebral hemorrhage (ICH) and attempted to reveal potential mechanisms of anterior ICH. Eligible adult MMD patients were consecutively included, and the morphological features of lenticulostriate arteries (LSAs), vessel wall structure of terminal internal carotid artery (ICA) and periventricular anastomosis were evaluated by HRMRI. 78 MMD patients containing 21 patients with anterior ICH, 31 ischemic patients and 26 asymptomatic patients were included. The mean value of total length of LSAs in anterior ICH group (90.79 ± 37.00 mm) was distinctively lower (p < 0.001) compared with either ischemic group (138.04 ± 46.01 mm) or asymptomatic group (170.50 ± 39.18 mm). Lumen area of terminal ICA was significantly larger (p < 0.001) in hemorrhagic group (4.33 ± 2.02 mm2) compared with ischemic group (2.29 ± 1.17 mm2) or asymptomatic group (3.00 ± 1.34 mm2). Multivariate analysis revealed the total length of LSAs (OR 0.689, 95%CI, 0.565–0.840; p < 0.001) and lumen area of terminal ICA (OR 2.085, 95%, 1.214–3.582; p = 0.008) were significantly associated with anterior ICH. Coexistence of reduced LSAs and relatively preserved lumen area of terminal ICA with an AUC of 0.901 (95%CI, 0.812–0.990) could be a potential predictor of anterior ICH in MMD patients.

TWIST1 silencing attenuates intracranial aneurysms by inhibiting NF-κB signaling

Purpose: To investigate the effect of Twist family basic helix-loop-helix transcription factor 1 (TWIST1) on intracranial aneurysms.Methods: A rat model of intracranial aneurysm was established by ligating the posterior branches of both the renal and left common carotid arteries. Pathological changes in the intracranial arterial wall were investigated using hematoxylin-eosin staining. TWIST1 expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, while vascular smooth muscle cell apoptosis was investigated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Inflammation was evaluated using enzyme-linked immunosorbent assay (ELISA).Results: Rats with intracranial aneurysms had degenerative changes in vessel wall structure. Inintracranial aneurysm rats, TWIST1 was upregulated in arterial wall sections, and TWIST1 knockdown ameliorated the pathological changes to the arterial wall. TWIST1 silencing reduced serum tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels and suppressed vascular smooth muscle cell apoptosis in rats with intracranial aneurysms. TWIST1 knockdown increased phospho (p)-inhibitor of nuclear factor-κB (IκB) and decreased IκB and p-p65 in intracranial aneurysm rat arterial wall sections.Conclusion: In intracranial aneurysms, silencing TWIST1 promoted vascular remodeling and suppresses vascular smooth muscle cell apoptosis and inflammation through inactivating NF-κBsignaling, revealing TWIST1 silencing as a potential treatment strategy.