Blood Vessel Wall Research Articles

In Situ Forming Supramolecular Nanofiber Hydrogel as a Biodegradable Liquid Embolic Agent for Postembolization Tissue Remodeling.

Embolic agents have been widely used to treat blood vessel abnormalities in interventional radiology as a minimally invasive procedure. However, only a few biodegradable liquid embolic agents exhibit high embolization performance, biodegradability, and operability. Herein, the design of in situ-forming supramolecular nanofiber (SNF) hydrogels is reported as biodegradable liquid embolic agents with the assistance of Bayesian optimization through an active learning pipeline. Chemically modified gelatin with hydrogen-bonding moieties produces fibrin-inspired nanofiber-based hydrogels with a high blood coagulation capacity. The low viscosity of the SNF hydrogels makes them injectable using a microcatheter, and the hydrogel shows sufficient tissue adhesion to the blood vessel walls and very weak adhesion to the catheter tubes. Moreover, the SNF hydrogels exhibit high blood compatibility, cytocompatibility, cell-adhesive properties, and biodegradability (in vitro and in vivo). Intravascularly delivered SNF hydrogels induce embolization of rat femoral arteries. This biodegradable liquid embolic agent could be a powerful tool for interventional radiology in the treatment of various diseases, including aortic aneurysm stent grafting, gynecological diseases, and liver cancer.

Coronary Artery Vasculitis and Encasement: Multimodality Imaging Findings and Mimics.

Coronary artery vasculitis (CAV) and coronary artery encasement are rarely diagnosed conditions that are important diagnostic considerations, particularly in patients with acute coronary syndrome without traditional cardiovascular risk factors or systemic illness. Vasculitis refers to inflammation of the blood vessel walls, which can be primary or secondary. This process should be distinguished from neoplastic involvement of the coronary arteries, termed coronary artery encasement. Prospective diagnosis of these diseases is challenging, often requiring multidisciplinary workup with careful attention to clinical presentation and multiorgan findings. While CAV and coronary artery encasement can be indistinguishable at coronary CT angiography, certain imaging features help order the differential diagnosis. CAV should be considered when there is smooth wall thickening that is circumferential and/or continuous. A diagnosis of coronary artery encasement is favored when there is irregular or nodular wall thickening that is eccentric to the vessel lumen. Epicardial fat stranding may also appear more extensive compared with CAV. Potential mimics of CAV include atherosclerosis, acute plaque rupture, coronary artery aneurysm, and spontaneous coronary artery dissection. Detection and diagnosis of CAV may help avoid complications related to accelerated atherosclerosis and infarction. Radiologists should be familiar with the range of pathologic conditions that can affect the coronary arteries beyond atherosclerosis as they may be the first to raise such diagnostic possibilities, guiding next steps in patient workup and management. ©RSNA, 2024 Supplemental material is available for this article.

The Detection of Chlamydia pneumoniae, Helicobacter pylori and Cytomegalovirus in Non-Atherosclerotic Arteries of Patients with Coronary Artery Disease

Atherosclerotic coronary artery disease (ACAD) is a major cause of global morbidity and mortality, characterized as an inflammatory process due to damage to blood vessel walls by risk factors like aging, hyperlipidemia, hypertension, smoking, and diabetes. Infectious agents, including Chlamydia pneumoniae (Cpn), Cytomegalovirus (CMV), and Helicobacter pylori (HP), have been implicated in ACAD’s pathophysiology. A study with 56 subjects undergoing coronary artery bypass grafting (CABG) aimed to detect Cpn, CMV, and HP DNA in unaffected artery segments and explore associations with disease progression and inflammation markers. The study found infectious agents’ DNA in 21.4% of samples, HP in eight samples, and CMV and Cpn in four samples each. Significant correlations were observed between HP and overweight or obese subjects, as well as between the presence of infectious agents and inflammation marker values. An association between HP and renal function was also noted. The findings reaffirm previous discoveries of infectious agents in non-clinically affected arteries used as CABG grafts. Correlations identified between the presence of HP, CMV, and Cpn DNA in grafts and several biomarkers of inflammation and obesity emphasize the potential role of these infectious agents in ACAD pathogenesis.

Impact of 6-OHDA injection and microtrauma in the rat substantia nigra on local brain amyloid beta protein concentrations in the affected area.

Amyloid beta peptides (Aβ) are key indicators of Alzheimer's disease and are also linked to cognitive decline in Parkinson's disease (PD) and other neurodegenerative disorders. This study explored the accumulation of Aβ in a standard 6-Hydroxydopamine (6-OHDA) model of PD. We unilaterally injected 6-OHDA into the substantia nigra of Wistar rats to induce dopaminergic cell degeneration and death, a characteristic of PD. The goal was to detect Aβ protein in tissues and blood vessels showing inflammation or degeneration from the 6-OHDA injection. Our results showed that 6-OHDA injection produced a statistically significant rise in Aβ concentration at the injection site 60 minutes after injection, which was slightly reduced 24 hours post-injection but still significantly higher than in controls. We also tried Gp120 injection in the same zone but it only produced effects comparable to control needle trauma. The presence of Aβ in tissues and blood vessel walls after injection was confirmed through ELISA tests and was supported by immunohistochemical staining of injection areas. We found that the increased Aβ concentration was visible in and around blood vessels and inside blood vessel walls, and also, to a lesser extent in some cells, most probably neurons, in the area. This research highlights the connection between dopaminergic cell poisoning and the accumulation of Aβ, offering insights into the progression of PD to cognitive disorders and dementia.

In situ visualization of endothelial cell-derived extracellular vesicle formation in steady state and malignant conditions.

Endothelial cells are integral components of all vasculature within complex organisms. As they line the blood vessel wall, endothelial cells are constantly exposed to a variety of molecular factors and shear force that can induce cellular damage and stress. However, how endothelial cells are removed or eliminate unwanted cellular contents, remains unclear. The generation of large extracellular vesicles (EVs) has emerged as a key mechanism for the removal of cellular waste from cells that are dying or stressed. Here, we used intravital microscopy of the bone marrow to directly measure the kinetics of EV formation from endothelial cells in vivo under homoeostatic and malignant conditions. These large EVs are mitochondria-rich, expose the 'eat me' signal phosphatidylserine, and can interact with immune cell populations as a potential clearance mechanism. Elevated levels of circulating EVs correlates with degradation ofthe bone marrow vasculature caused by acute myeloid leukaemia. Together, our study provides in vivo spatio-temporal characterization of EV formation in the murine vasculature and suggests that circulating, large endothelial cell-derived EVs can provide a snapshot of vascular damage at distal sites.

A Review on Venous Thrombosis: Management with anticoagulants

Thrombosis is the most common condition and the world's leading cause of death due to blood clot development in blood arteries. Thromboembolism includes classification based on where the thrombus gets attached to the blood vessels. Deep vein thrombosis (DVT) and pulmonary embolism (PE) are two of the main causes of vascular death globally, making up venous thromboembolism (VTE). According to estimates, the yearly incidence rates of VTE in individuals with European ancestry vary from 104 to 183 per 100,000 person-years. Thrombus development and propagation are dependent upon the existence of anomalies in blood flow, blood vessel wall, and blood clotting components, which are together referred to as Virchow's triad. A comprehensive diagnostic approach, which includes clinical evaluation, D-dimer testing, ultrasonography, and lung scan, provided a non-invasive diagnosis for most outpatients with suspected venous thromboembolism. Anticoagulant medication is the primary and established treatment for people who have acute venous thromboembolism (VTE). Among the treatment options available, UFH & LMWH are found to be safe for the growing fetus as they appear to not cross the placenta. Oral anticoagulants targeting thrombin or factor Xa have been introduced, replacing vitamin K antagonists. In a study involving DOACs vs VKAs in patients with pre-existing heart conditions, patients receiving DOACs for non-valvular atrial fibrillation had predominantly superior efficacy and safety. Keywords: Venous thromboembolism, Anticoagulants, Deep vein thrombosis, Pulmonary embolism, Thrombus

Analytical solution of a microrobot-blood vessel interaction model

AbstractThis study develops a dynamics model of a microrobot vibrating in a blood vessel aiming to detect potential cancer metastasis. We derive an analytical solution for microrobot’s motion, considering interactions with the vessel walls modelled by a linear spring-dashpot and a constant damping value for blood viscosity. The model facilitates instantaneous state transitions of the microrobot, such as contact with the vessel wall and free motion within the fluid. Amplitudes and phase angles from the transient solutions of dynamics model of the microrobot are solved at arbitrary moments, providing insights into its transient dynamics. The analytical solution of the proposed system is validated by experimental data, serving as a benchmark to examine the influence of pertinent parameters on microrobot’s dynamic response. It is found that the contact force transmitted to the vessel wall, assessed by system’s transmissibility function dependent on damping and frequency ratios, decreases with increasing damping ratio and intensifies when the frequency ratio is below $$\sqrt 2$$ 2 . At the frequency ratio is equal to 1, resonance phenomenon is dominated by the magnification factor linked to the damping ratio, increasing the amplitude of resonance as damping decreases. Finally, different sets of system parameters, including excitation frequency and magnitude, fluid damping, vessel wall’s stiffness and damping, reveal multi-periodic motions and fake collision of the microrobot with the vessel wall. Simulation results imply that these phenomena are minimally affected by vessel wall’s stiffness but are significantly influenced by other parameters, such as fluid damping coefficient and damping coefficient of the blood vessel wall. This research provides a robust theoretical foundation for developing control strategies for microrobots aimed at detecting cancer metastasis.

Optimization and Application Analysis of Phase Correction Method Based on Improved Image Registration in Ultrasonic Image Detection

ABSTRACTIn order to prevent and detect a wide range of disorders, including those of the brain, thoracic, digestive, urogenital, and cardiovascular systems, ultrasound technology is essential for assessing physiological data and tissue morphology. Its capacity to deliver real‐time, high‐frequency scans makes it a handy and non‐invasive diagnostic tool. However, issues like patient movements and probe jitter from human error can provide a large amount of interference, resulting in inaccurate test findings. Techniques for image registration can assist in locating and eliminating unwanted interference while maintaining crucial data. Even though there has been research on improving these techniques in Matlab, there are no specialized systems for interference removal, and the procedure is still time‐consuming, particularly when working with huge quantities of ultrasound images. The phase correlation technique, which converts images into the frequency domain and makes noise suppression easier, is one of the most efficient algorithms now in use since it can tolerate noise with resilience. Nevertheless, little research has been done on using this technique to identify displacement in blood vessel wall ultrasound images. To address these gaps, this work presents an image registration system that uses the phase correlation algorithm. The system provides rotation, zoom registration, picture translation, and displacement detection of the vessel wall in addition to interference removal. Furthermore, batch processing is included to increase the effectiveness of registering multiple ultrasound pictures. Through efficient interference management and streamlined registration, this method offers a workable way to improve the precision and efficacy of ultrasonic diagnostics.

There is poor agreement between the subjective and quantitative adjudication of aneurysm wall enhancement.

The determination of Aneurysm wall enhancement (AWE) by human readers on visual inspection alone is subjective and prone to error. A three-dimensional (3D) method for quantifying the aneurysm wall's signal intensity (SI) enables objective determination of AWE. Inter-reader agreement and agreement between subjective and objective determination of AWE were assessed in this study. Patients with saccular intracranial aneurysms (IAs) were imaged with high-resolution MRI. Subjective assessment: Two internal adjudicators visually determined AWE if the degree of enhancement was equal to or higher than the pituitary stalk. An experienced internal neuroradiologist resolved disagreements. This internal adjudication was compared with an external adjudication to assess inter-rater agreement among centers. Objective assessment: The distribution of SI across the aneurysm wall after normalizing the SI to the corpus callosum was determined with an in-house code. The normalized mean SI on post-contrast T1 MRI was defined as 3D-circumferential AWE (3D-CAWE). If the 3D-CAWE value was higher than one, an IA was defined as objectively "enhancing." Inter-rater agreement was analyzed with kappa coefficients. Inter-technique agreement between subjective and objective assessment was performed using kappa statistics. Univariate regressions were performed to identify which morphological characteristics influenced subjective adjudication of enhancement. A total of 113 IAs were analyzed. The agreement of the internal assessment was moderate (k = 0.63), 49.5% of IAs (56) were classified as "enhancing" and 50.5% (57) as "non-enhancing" after consensus. Inter-rater agreement between internal and external adjudication was weak (k = 0.52) for the presence of AWE. There was no agreement between the subjective assessment of AWE and objective 3D-CAWE (k = 0.16, p 0.02). Subjective assessment was less likely to reliably adjudicate enhancement when assessing multiple aneurysms (OR 0.4, 95% CI 0.16 -0.97, p 0.04) and IAs larger than > 7 mm (OR 0.22, 95% CI 0.09 -0.55, p 0.002) despite being objectively "non-enhancing". Subjective adjudication of AWE has poor inter-rater agreement, and no agreement with an objective 3D method of determining AWE. It is also less likely than objective quantification to identify enhancement in aneurysms larger than 7 mm or when multiple aneurysms are present. Objective 3D quantification, such as the technique used in this study, should therefore be considered when assessing AWE, especially in patients with multiple aneurysms and aneurysms larger than 7 mm in size. 3D, three-dimensional; 3D-CAWE, three-dimensional circumferential aneurysm wall enhancement; AWE, aneurysm wall enhancement; Gd, gadolinium; HR-MRI, high resolution MRI; HR 3D T1 VWI, high-resolution 3D T1 weighted black blood vessel wall imaging; IA, intracranial aneurysm; SI, signal intensity.

Investigation of TLR4, TLR6, TLR7, and CD36 expression on T lymphocytes in coronary artery disease

Background: Coronary artery disease (CAD) is among the significant causes of death globally, caused by fatty deposits in blood vessel walls. Increasing evidence indicates that toll-like receptors (TLRs) are pivotal to atherosclerosis progression. The function of CD36 as a glycoprotein in atherosclerosis was also suggested. This study aimed to investigate the levels of TLR4, TLR6, and TLR7, as well as CD36 cell surface markers in CAD. Methods: This study included 64 patients undergoing angiography to determine whether atherosclerosis was present. The patients were categorized into two groups. The three main coronary arteries are all stenosed at over 50% in patients with CAD+ (n=22) as cases and CAD− (n=42) with smooth angiography as controls. Each patient's syntax score (SS) and Gensini (vessel score) were calculated. The TLR-4, TLR-6, TLR-7, and CD36 expression were measured using Flow cytometry. Results: TLR4 and TLR6 showed a significant link with the Gensini score in the subject group. In addition, TLR7 had an association with Syntax scoring in this study. Conclusion: The findings illustrated the association between TLR4, TLR6, and TLR7 cell surface markers with Gensini and Syntax scoring in individuals with coronary artery disease.

Super-Microsurgery for Vessels with Diameters Smaller Than 0.5 mm.

Introduction: Among super-microsurgical techniques, the anastomosis of vessels smaller than 0.5 mm is very difficult to perform due to the small diameter and thinness of the blood and lymphatic vessel walls. In this article, we report on the main points of super microsurgery, particularly on the anastomosis of veins and lymphatic vessels with diameters smaller than 0.5 mm. Methods and Results: Details of anastomosis of vessels smaller than 0.5 mm. (1) The outer wall of the first blood vessel near the abrupt end hook with the tip of the needle in the needle holder. The entire abrupt end of the first blood vessel was supported by forceps in the surgeon's left-hand. (2) The surgeon decided the entry point and angle of the needle while moving the tip. After the needle was fixed, a force was applied so that the needle could pass through to the vascular wall. (3) After the needle passed through, the tip was confirmed to be located in the lumen of the first blood vessel. (4) The tip of the needle was inserted into the lumen of the second blood vessel, and the bite was adjusted while touching the second blood vessel through the endometrium. (5) Once the tip was properly positioned, counter-traction was applied by holding the entire outer wall with a left-hand forceps. (6) The needle was held near the tip and pulled out along its curvature. The anastomosis time was 11.35 minutes on average (9 to 14 minutes). The patency rate for all 20 anastomosis procedures was also 100%. Conclusion: The important points of LVA for lymphatic vessels and veins smaller than 0.5 mm were reported. Once the surgeons are familiarized with this anastomosis procedure, they can typically perform one anastomosis in about 10 minutes.

Clinicopathological and genetic analysis of interstitial disease-like pulmonary intravascular large B cell lymphoma

Objective: To investigate the clinicopathological features and genetic mutation status of pulmonary intravascular large B cell lymphoma. Methods: The clinicopathological data of eight patients diagnosed with pulmonary intravascular large B cell lymphoma, from April 2018 to May 2023, were retrospectively analyzed. The genetic profile of six patients was detected via next-generation sequencing (NGS) and followed up. Results: All patients included one male and seven females, with a median age of 64 years (ranging from 45 to 66 years). Respiratory symptoms were the most common (7 cases), B symptoms in two cases, hemophagocytic syndrome in two cases. Multiple diffuse ground-glass opacities in both lungs were observed based on the high-resolution chest CT scan. Six cases of mild to moderate ventilation or diffusion dysfunction were observed based on the pulmonary function tests. Moreover, two cases of hypoxemia and two cases with type Ⅰ respiratory failure were recorded. The serum lactate dehydrogenase level increased (7/8), β2-MG level increased (2/8), neuron-specific enolase level increased (7/8), total number of peripheral blood lymphocytes decreased (7/8), and clinical stages were all stage Ⅳ. The neoplastic lymphoid cells were lodged in the lumina of venules and capillaries of the alveolar septum; the tumor cells were large, with prominent nucleoli and frequent mitotic figures. The malignant cells were detected in the extravascular surrounding lung tissue in all cases. The tumor cells expressed mature B cell-associated antigens CD20 and CD79a, and the vascular endothelial markers CD31 and CD34 showed that the tumor cells were filled in the blood vessels, infiltrated blood vessel walls, and perivascular areas. One case was germinal center-type, seven cases were non-germinal center-type, two cases were double-expressing lymphoma, and all cases were EBER-negative. Furthermore, the top five genes with mutation frequencies detected by NGS were MYD88 (5/6), PIM1 (5/6), CD79B (4/6), TCF3 (4/6), and TP53 (3/6). Of the eight cases, seven patients received R-CHOP-based chemotherapy, six cases had complete remission after chemotherapy, one case died, and one case was lost to follow-up. Conclusions: Pulmonary vascular large B cell lymphoma is rare, which shares similar patterns with interstitial lung disease on imaging. Transbronchial lung biopsy is an effective method to confirm the diagnosis. Immunochemotherapy with BTK inhibitors can provide a survival advantage for patients in the future based on molecular typing.

THE THERAPEUTIC POTENTIAL OF PRECONDITIONED MESENCHYMAL STEM CELLS IN ATHEROSCLEROSIS

Atherosclerosis (AS) is a multifactorial and inflammatory disease the cause of which is the formation of lipid and cholesterol plaques on the inner wall of blood vessels. Experimental and clinical studies have shown that the pathogenesis of atherosclerosis is, in particular, connected with inflammatory reactions. Recent studies reported that preconditioned mesenchymal stem cells (MSCs) possess an enhanced immunomodulatory potential. The purpose of the study was to investigate the therapeutic potential of preconditioned MSCs in the development of atherosclerosis. MSCs were isolated from the compact bone of mice by standard protocol. The characterization was conducted using flow cytometry, CFU assay and three-lineage differentiation. Cells were preconditioned with different combinations of cytokines and the optimal concentrations were determined by ELISA and by analysis of co-culturing with lymphocytes. The cytokine-preconditioned MSCs were administrated to mice with induced atherosclerosis. The lipids analysis, measuring of mouse spleens’ weights, ELISA and histological analysis of the aorta sections were done after 8-th weeks. We isolated MSCs and then confirmed the possession of the immunomodulatory properties. Preconditioning with the TNF-α cytokine effectively increased the immunomodulatory properties of MSCs compared to untreated MSCs in vitro. The results of in vivo study that the use of TNF-α-preconditioned MSCs reduced the development of atherosclerosis in mice compared to untreated MSCs: it increased the level of Treg cells in the spleen of mice; significantly reduced the levels of TNF-α and IFN-γ in blood serum; significantly reduced the spleen weights of mice; slightly decreased the total cholesterol levels and also increased HDL levels. Administration of TNF-α-preconditioned MSCs reduced the size of atherosclerotic plaques in the aorta of mice. The results of this study demonstrated the effect of cytokine-preconditioned MSCs in the inhibition of the development of atherosclerosis in a mouse model. However, for application as a therapy for suffered patients additional studies are needed. Besides, using of TNF-α preconditioned MSCs can be considered in other preclinical studies of the different diseases.

Human Endometrial Pericytes: A Comprehensive Overview of Their Physiological Functions and Implications in Uterine Disorders.

Pericytes are versatile cells integral to the blood vessel walls of the microcirculation, where they exhibit specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, and maintaining homeostasis and are involved in the tissue repair process. The human endometrium is a unique and complex tissue that serves as a natural scar-free healing model with its cyclical repair and regeneration process every month. The regulation of pericytes has gained increasing attention due to their involvement in various physiological and pathological processes. However, endometrial pericytes are less well studied compared to the pericytes in other organs. This review aims to provide a comprehensive overview of endometrial pericytes, with a focus on elucidating their physiological function and potential implications in uterine disorders.

Sialyl Lewis X decorated integrin α3 on small extracellular vesicles promotes metastasis of bladder cancer via enhancing vascular permeability.

The permeability of blood vessels plays a crucial role in the spread of cancer cells, facilitating their metastasis at distant sites. Small extracellular vesicles (sEVs) are known to contribute to the metastasis of various cancers by crossing the blood vessel wall. However, the role of abnormal glycoconjugates on sEVs in tumor blood vessels remains unclear. Our study found elevated levels of fucosyltransferase VII (FUT7) and its product sialyl Lewis X (sLeX) in muscle-invasive bladder cancer (BLCA), with high levels of sLeX promoting the growth and invasion of BLCA cells. Further investigation revealed that sLeX was enriched in sEVs derived from BLCA. sLeX-decorated sEVs increased blood vessel permeability by disrupting the tight junctions of human umbilical vein endothelial cells (HUVECs). Using the glycoproteomics approach, we identified integrin α3 (ITGA3) as a sLeX-bearing glycoprotein in BLCA cells and their sEVs. Mechanically, sLeX modification stabilized ITGA3 by preventing its degradation in lysosomes. sEVs carrying sLeX-modified ITGA3 can be effectively internalized by HUVECs, leading to a decrease in the expression of tight junction protein. Conversely, silencing ITGA3 in sLeX-decorated sEVs restored tight junction proteins and reduced blood vessel permeability by inhibiting the MAPK pathway. Moreover, sLeX-modification of ITGA3 at Asn 265 in HUVECs promoted occludin dephosphorylation at Ser/Thr residues, followed by inducing its importin α1-mediated nuclear translocation, which resulted in the disruption of tight junctions. Our findings suggest a potential strategy for disrupting the formation of a metastatic microenvironment and preventing the spread of malignant bladder cancer.

Three-Dimensionally Printed Elastic Cardiovascular Phantoms for Carotid Angioplasty Training and Personalized Healthcare.

Background/Objective: Atherosclerosis is becoming increasingly common in modern society. Owing to the increasing number of complex angioplasty procedures, there is an increasing need for training in cases where the risk of periprocedural complications is high. Methods: A procedure was developed to obtain three-dimensional (3D) models and printing of blood vessels. The mechanical and optical properties of the printed materials were also examined. Angioplasty and stent implantation were tested, and the phantom was compared with the clinical data of patients who underwent interventional treatment. Both laser techniques and cone-beam computed tomography of the phantoms were used for comparison. Results: The printed material exhibited mechanical parameters similar to those of blood vessel walls. The refractive index of 1.473 ± 0.002 and high transparency allowed for non-invasive laser examination of the interior of the print. The printed models behaved similarly to human arteries in vivo, allowing training in treatment procedures and considering vessel deformation during the procedure. Models with stents can be analyzed using laser and cone-beam computed tomography to compare stents from different manufacturers. Conclusions: The developed methodology allows for simple and time-efficient production of personalized vessel phantoms.

THE RELATIONSHIP OF SMOKING HABITS WITH HYPERTENSION INCIDENCE IN MEN AGE 20-40 YEARS IN THE WORK AREA OF THE BINTARA HEALTH CENTER

Hypertension is a non-communicable disease until now dubbed as The Silent Killer because the symptoms are unknown and even often do not show symptoms without complaints. Hypertension is a condition in which a person's blood pressure, systolic ≥140 mmHg and diastolic ≥90 mmHg. Hypertension at the age of 20-44 years, especially in men, the main cause is a lifestyle such as smoking Smoking is one of the risk factors that can cause an increase in blood pressure. Cigarettes contain 400 chemical substances with 200 types of them being carcinogenic. Carbon monoxide and nicotine gases produced by cigarettes, cause the walls of blood vessels to narrow so that the heart has to pump faster and blood pressure increases significantly.

MYH11 rare variant augments aortic growth and induces cardiac hypertrophy and heart failure with pressure overload.

Smooth muscle cell-specific myosin heavy chain, encoded by MYH11, is selectively expressed in smooth muscle cells (SMCs). Pathogenic variants in MYH11 predispose to a number of disorders, including heritable thoracic aortic disease associated with patent ductus arteriosus, visceral myopathy, and megacystis-microcolon-intestinal hypoperistalsis syndrome. Rare variants of uncertain significance occur throughout the gene, including MYH11 p.Glu1892Asp, and we sought to determine if this variant causes thoracic aortic disease in mice. Genomic editing was used to generate Myh11 E1892D/E1892D mice. Wild-type (WT) and mutant mice underwent cardiovascular phenotyping and with transverse aortic constriction (TAC). Myh11 E1892D/E1892D and WT mice displayed similar growth, blood pressure, root and ascending aortic diameters, and cardiac function up to 13 months of age, along with similar contraction and relaxation on myographic testing. TAC induced hypertension similarly in Myh11 E1892D/E1892D and WT mice, but mutant mice showed augmented ascending aortic enlargement and increased elastic fragmentation on histology. Unexpectedly, male Myh11 E1892D/E1892D mice two weeks post-TAC had decreased ejection fraction, stroke volume, fractional shortening, and cardiac output compared to similarly treated male WT mice. Importantly, left ventricular mass increased significantly due to primarily posterior wall thickening, and cardiac histology confirmed cardiomyocyte hypertrophy and increased collagen deposition in the myocardium and surrounding arteries. These results further highlight the clinical heterogeneity associated with MYH11 rare variants. Given that MYH11 is selectively expressed in SMCs, these results implicate a role of vascular SMCs in the heart contributing to cardiac hypertrophy and failure with pressure overload.

Abstract Tu014: Endoplasmic reticulum stress exacerbates atherosclerosis via microRNA-181a by inhibiting mitophagy

Introduction: Atherosclerosis is a chronic and progressively advancing vascular disease, which ultimately leads to the hardening and narrowing of blood vessel walls, significantly increasing the risk of cardiovascular events such as heart attacks and strokes. Within plaques, macrophages undergo endoplasmic reticulum stress(ERS) in response to lipid stimulation, directly impacting mitochondrial function. Mitophagy serves as the primary pathway for macrophages to clear damaged mitochondria. However, the relationship between endoplasmic reticulum stress in macrophages and mitophagy remains unclear. Hypothesis: there exists a regulatory relationship between endoplasmic reticulum stress and mitophagy in macrophages. Objective: To study the effect of endoplasmic reticulum stress on mitophagy and its mechanism in atherosclerosis. Methods: To investigate the effect of ERS on mitochondrial autophagy, we specifically inhibited IRE1α activity in vivo, followed by testing atherosclerosis plaque and mitophagy. To explore the mechanism by which endoplasmic reticulum stress acts on mitophagy, we detected miRNAs by qPCR. The Binding of Inositol-requiring enzyme 1(IRE1α) to miRNA was detected by RNA Binding Protein Immunoprecipitation Assay (RIP). We verified miRNA’s effect on regulating mitophagy by knocking down or over expressing miRNA in vivo. To find the downstream mechanism, we predicted and verified the target gene and testified the signaling pathway by rescue experiments. Results: IRE1α RNase activity inhibition lightened atherosclerosis but upregulated miRNA181a and mitophagy level. In vivo, overexpressing miRNA181a reduced atherosclerosis plaque and enhanced mitophagy; results were reversed when knocking down miRNA181a. Overexpressing or silencing target gene in vitro, mitophagy is correspondingly inhibited or promoted. Conclusion: In atherosclerosis, endoplasmic reticulum stress increases, resulting in inhibition of mitophagy. IRE1 α further increases its target gene JNK by shearing pre-miRNA181, thereby inhibiting the expression of miRNA181a. The over expression of JNK eventually upregulated the JNK-c-JUN-Parkin signaling pathway, aggravating atherosclerosis. These results provided new data for the mechanism of endoplasmic reticulum stress on atherosclerosis.

Surgical technique and effect of the pulsatile tinnitus associated with sigmoid sinus on the dominant side of reflux

Objective:To explore the effect of surgical treatment of the pulsatile tinnitus associated with sigmoid sinus on the dominant side of reflux. Methods:The clinical data of 43 patients with reflux dominant side pulsating tinnitus admitted by the same doctor from 2017 to 2023 were retrospectively studied to observe the curative effect of surgical treatment. Operation method: The sound insulation barrier was established by repair technique of bone wall defect of sigmoid sinus with "capping method", without changing the blood flow and blood vessel wall of sigmoid sinus. Results:No surgical complications occurred in all patients. During the follow-up period of 3 months to 6.9 years, 14 patients（32.6%） were cured, 18 patients（41.9%） were significantly effective, 4 patients（9.3%） were effective, and 7 patients（16.3%） were ineffective. The difference of tinnitus grade before and after surgery was statistically significant. Conclusion:In this group of cases, the sound insulation barrier was established by "capping method" technique of repairing bone wall defect of sigmoid sinus, which effectively avoided the disturbance of hemorheology status and vascular wall, thus avoiding the risk of venous wall stenosis and thrombosis on the dominant reflux side. The surgical method was easy to master, and the curative effect was significant, which was worthy of clinical promotion.