Lessons from autopsy: Topographical variability of atherosclerosis plaques.

Atherosclerosis is a complex disease characterized by the accumulation of plaques in arterial walls. Understanding its pathogenesis remains incomplete, with factors like inflammation, oxidative stress, and hypertension playing critical roles. The disease exhibits preferential localization of plaques, with variability observed even within the same individual. Genetic, environmental, and lifestyle factors contribute to its heterogeneity. Histological plaque phenotypes vary widely, prompting classification schemes focusing on systemic and local factors deteriorating fibrous caps. Recent research highlights differences in plaque histology among arterial systems, suggesting unique pathophysiological mechanisms. This study reports on multiple atherosclerotic plaques detected at autopsy in various vascular sites of a single subject, emphasizing their histological diversity and underscoring the systemic nature of atherosclerosis.

Evolutionary trends and innovations in cardiovascular intervention.

Cardiovascular diseases remain a global health challenge, prompting continuous innovation in medical technology, particularly in Cardiovascular MedTech. This article provides a comprehensive exploration of the transformative landscape of Cardiovascular MedTech in the 21st century, focusing on interventions. The escalating prevalence of cardiovascular diseases and the demand for personalized care drive the evolving landscape, with technologies like wearables and AI reshaping patient-centric healthcare. Wearable devices offer real-time monitoring, enhancing procedural precision and patient outcomes. AI facilitates risk assessment and personalized treatment strategies, revolutionizing intervention precision. Minimally invasive procedures, aided by robotics and novel materials, minimize patient impact and improve outcomes. 3D printing enables patient-specific implants, while regenerative medicine promises cardiac regeneration. Augmented reality headsets empower surgeons during procedures, enhancing precision and awareness. Novel materials and radiation reduction techniques further optimize interventions, prioritizing patient safety. Data security measures ensure patient privacy in the era of connected healthcare. Modern technologies enhance traditional surgeries, refining outcomes. The integration of these innovations promises to shape a healthier future for cardiovascular procedures, emphasizing collaboration and research to maximize their transformative potential.

Relationship Between Hypertension and Hearing Loss: Analysis of the Related Factors.

Purpose: The impact of hypertension extends to hearing loss, aging, and mental Health. The purpose of this study was to investigate the characteristics of hearing loss and hearing thresholds at different frequencies in individuals with hypertension. Through a comprehensive analysis, in the present study, it aimed to uncover the contributing factors that underlie hearing loss in this patient cohort, shedding light on the complex relationship between hypertension and auditory impairment. Patients and Methods: This was a single-center population-based observational study, and clinical, biological, and hospital data were collected from the inpatient ward. In the present study, 517 patients (1034 ears) with or without hypertension were included, and the proportion of patients with hearing loss, mean pure-tone average hearing threshold, low-frequency pure-tone average hearing threshold (LFPTA), medium-frequency pure-tone average hearing threshold (MFPTA) and high-frequency pure-tone average hearing threshold (HFPTA) were evaluated. Risk factors related to hearing loss and hearing threshold were also estimated at different frequencies. Results: The proportion of patients with hearing loss was higher in the hypertensive group than in the nonhypertensive group (P<0.05). After including risk factors for cardiovascular disease that can have an impact on the parameters of hearing and ambulatory blood pressure in the regression model, factors related to hearing loss included the albumin-to-creatinine ratio (ACR) and the standard deviation of the 24-hour systolic blood pressure (24h-SSD). ACR, 24h-SSD, and day systolic blood pressure (Day SBP) were associated with the mean pure-tone average hearing threshold, LFPTA, MFPTA, and HFPTA. The area under the receiver operating characteristic curve of ACR + 24h-SSD for hearing loss was 0.873, with a sensitivity of 86.73%, specificity of 90.52%, and a 95% confidence interval of 0.821-0.914. Conclusion: Hypertension is correlated with hearing loss, and the combination of ACR and 24h-SSD demonstrates an improved predictive capacity for hearing loss in hypertensive patients.

Vascular Alterations Following COVID-19 Infection: A Comprehensive Literature Review.

SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, has revealed a broader impact beyond the respiratory system, predominantly affecting the vascular system with various adverse manifestations. The infection induces endothelial dysfunction and immune system dysregulation, creating an inflammatory and hypercoagulable state. It affects both microvasculature and macrovasculature, leading to thromboembolic events, cardiovascular manifestations, impaired arterial stiffness, cerebrovascular complications, and nephropathy, as well as retinopathy-frequently observed in cases of severe illness. Evidence suggests that SARS-CoV-2 infection may result in persistent effects on the vascular system, identified as long-term COVID-19. This is characterized by prolonged inflammation, endotheliopathy, and an increased risk of vascular complications. Various imaging modalities, histopathological studies, and diagnostic tools such as video capillaroscopy and magnetic resonance imaging have been employed to visualize vascular alterations. This review aims to comprehensively summarize the evidence concerning short and long-term vascular alterations following COVID-19 infection, investigating their impact on patients' prognosis, and providing an overview of preventive strategies to mitigate associated vascular complications.

Safety of Anti-Reelin Therapeutic Approaches for Chronic Inflammatory Diseases.

Reelin, a large extracellular glycoprotein, plays critical roles in neuronal development and synaptic plasticity in the central nervous system (CNS). Recent studies have revealed non-neuronal functions of plasma Reelin in inflammation by promoting endothelial-leukocyte adhesion through its canonical pathway in endothelial cells (via ApoER2 acting on NF-κB), as well as in vascular tone regulation and thrombosis. In this study, we have investigated the safety and efficacy of selectively depleting plasma Reelin as a potential therapeutic strategy for chronic inflammatory diseases. We found that Reelin expression remains stable throughout adulthood and that peripheral anti-Reelin antibody treatment with CR-50 efficiently depletes plasma Reelin without affecting its levels or functionality within the CNS. Notably, this approach preserves essential neuronal functions and synaptic plasticity. Furthermore, in mice induced with experimental autoimmune encephalomyelitis (EAE), selective modulation of endothelial responses by anti-Reelin antibodies reduces pathological leukocyte infiltration without completely abolishing diapedesis. Finally, long-term Reelin depletion under metabolic stress induced by a Western diet did not negatively impact the heart, kidney, or liver, suggesting a favorable safety profile. These findings underscore the promising role of peripheral anti-Reelin therapeutic strategies for autoimmune diseases and conditions where endothelial function is compromised, offering a novel approach that may avoid the immunosuppressive side effects associated with conventional anti-inflammatory therapies.

Flavan-3-ols, flavonoids, anthocyanidins and triterpenoids induces TIE2 phosphorylation -a candidate target for the vascular protective effects.

Vascular system is essential for the body to maintain health. Dysregulated vascular system leads to cardiovascular diseases and are observed in ischaemic stroke, Alzheimer's disease, amyotrophic lateral sclerosis, and diabetes. TIE2 is a tyrosine kinase receptor expressed on vascular endothelial cells and contributes to the maintenance of a vascular system. In this paper, we screened for natural products with an activity to induce phosphorylation of TIE2, which will be beneficial for protection of a vascular system. Employing HeLa cells expressing TIE2, flavan-3-ols, flavonoids, anthocyanidins and triterpenoids were identified as active compounds that induce TIE2 phosphorylation. Several of the identified compounds are previously reported to protect endothelial cells from inflammation. Thus, the result provided TIE2 as the candidate receptor protein of those compounds for the protective effect of endothelial cells and the identified compounds will be a good candidate for maintenance of a vascular system.

Intraoperative Corticosteroids and Pacemaker Implantation After Transcatheter Aortic Valve Replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of aortic stenosis. However, conduction disturbances leading to pacemaker implantation remain a common complication, increasing morbidity and mortality in these patients. Hence, measures to lower its incidence should be taken, and corticosteroid therapy could be effective by reducing inflammation caused by direct mechanical trauma to the conduction system. METHODS: A retrospective cohort study was conducted at the Centro Hospitalar de Vila Nova de Gaia/Espinho, analyzing the medical records of patients with native severe aortic stenosis who underwent transfemoral TAVR in 2022. The Chi-square test was used to compare the rate of pacemaker implantation in patients who received corticosteroids with patients who didn't. The statistical significance was considered for a p-value <0.05. RESULTS: A total of 341 patients were included in this study. Monitored anesthesia care was the preferred anesthetic technique (99.1%). Sixty-three point three percent (63.3%) of patients received corticosteroids at the beginning of the procedure. Corticosteroid administration did not significantly affect the incidence of permanent pacemaker implantation (p=0.277), vascular complications on the access site (p=0.765), or in-hospital mortality (p=0.909). Male gender, 1st-degree atrioventricular block, and right branch block were the only identified predictors of permanent pacemaker implantation after transfemoral TAVR (p=0.041 <0.001 and <0.001, respectively). CONCLUSION: Corticosteroid administration at the beginning of TAVR doesn't seem to influence the incidence of permanent pacemaker implantation, which can suggest that other factors play a more important role in the development of conduction disturbances leading to pacemaker implantation.

Characterization of Vascular Niche in Systemic Sclerosis by Spatial Proteomics.

BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease that can serve as a model to study vascular changes in response to inflammation, autoimmunity, and fibrotic remodeling. Although microvascular changes are the earliest histopathologic manifestation of SSc, the vascular pathophysiology remains poorly understood. METHODS: We applied spatial proteomic approaches to deconvolute the heterogeneity of vascular cells at the single-cell level in situ and characterize cellular alterations of the vascular niches of patients with SSc. Skin biopsies of patients with SSc and control individuals were analyzed by imaging mass cytometry, yielding a total of 90 755 cells including 2987 endothelial cells and 4096 immune cells. RESULTS: We identified 7 different subpopulations of blood vascular endothelial cells (VECs), 2 subpopulations of lymphatic endothelial cells, and 3 subpopulations of pericytes. A novel population of CD34+;αSMA+ (α-smooth muscle actin);CD31+ VECs was more common in SSc, whereas endothelial precursor cells were decreased. Co-detection by indexing and tyramide signal amplification confirmed these findings. The microenvironment of CD34+;αSMA+;CD31+ VECs was enriched for immune cells and myofibroblasts, and CD34+;αSMA+;CD31+ VECs expressed markers of endothelial-to-mesenchymal transition. The density of CD34+;αSMA+;CD31+ VECs was associated with clinical progression of fibrosis in SSc. CONCLUSIONS: Using spatial proteomics, we unraveled the heterogeneity of vascular cells in control individuals and patients with SSc. We identified CD34+;αSMA+;CD31+ VECs as a novel endothelial cell population that is increased in patients with SSc, expresses markers for endothelial-to-mesenchymal transition, and is located in close proximity to immune cells and myofibroblasts. CD34+;αSMA+;CD31+ VEC counts were associated with clinical outcomes of progressive fibrotic remodeling, thus providing a novel cellular correlate for the crosstalk of vasculopathy and fibrosis.

Friction injury of the central vein caused by catheter for hemodialysis: an in vitro study.

Vascular injury such as central venous stenosis (CVS) is a common complication in hemodialysis patients with central venous catheters (CVCs), yet the impact of the microstructure and partial physic characteristics of catheter surface on the chronic injury of central vein has not been elucidated. In this study, the microscopic morphology of tips and bodies of six different brands of polyurethane CVCs was observed and their roughness was assessed. Subsequently, an in vitro model was established to measure the coefficients of friction (COF) between CVCs (tips and bodies) and the vena cava intima of Japanese rabbits under the same condition in a linear reciprocating mode, and changes in the intima of vessels after friction were observed. The study found that there was a significant variation in surface roughness among different brands of CVCs (tips P < 0.001, bodies P = 0.02), and the COF was positively correlated with the catheter surface roughness (tips P = 0.005, R = 0.945, bodies P = 0.01, R = 0.909). Besides, the endovascular roughness increased after friction. These findings suggest that the high roughness surface of CVCs may cause chronic mechanical friction injury to the central venous intima, which is one of the potential factors leading to CVS or occlusion. This provides a breakthrough for reducing complications, improving patient prognosis, and advancing catheter surface lubrication technology.

Human pluripotent stem cell-derived kidney organoids: Current progress and challenges.

Human pluripotent stem cell (hPSC)-derived kidney organoids share similarities with the fetal kidney. However, the current hPSC-derived kidney organoids have some limitations, including the inability to perform nephrogenesis and lack of a corticomedullary definition, uniform vascular system, and coordinated exit pathway for urinary filtrate. Therefore, further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development, regeneration, disease modeling, and drug screening. In this review, we discussed recent advances in the generation of hPSC-derived kidney organoids, how these organoids contribute to the understanding of human kidney development and research in disease modeling. Additionally, the limitations, future research focus, and applications of hPSC-derived kidney organoids were highlighted.

Vascular microforamina and endocranial surface: Normal variation and distribution in adult humans: Vascular biology.

The term craniovascular traits refers to the imprints left by arteries and veins on the skull bones. These features can be used in biological anthropology and archaeology to investigate the morphology of the vascular network in extinct species and past populations. Generally, the term refers to macrovascular features of the endocranial cavity, like those associated with the middle meningeal artery, venous sinuses, emissary foramina, and diploic channels. However, small vascular passages (here called microforamina or microchannels) have been occasionally described on the endocranial surface. The larger ones (generally with a diameter between 0.5 and 2.0 mm) can be detected through medical scanners on osteological collections. In this study, we describe and quantify the number and distribution of these microforamina in adult humans (N = 45) and, preliminarily, in a small sample of children (N = 7). Adults display more microchannels than juvenile skulls. A higher frequency in females is also observed, although this result is not statistically significant and might be associated with allometric cranial variations. The distribution of the microforamina is particularly concentrated on the top of the vault, in particular along the sagittal, metopic, and coronal sutures, matching the course of major venous sinuses and parasagittal bridging veins. Nonetheless, the density is lower in the region posterior to bregma. Beyond oxygenation, these vessels are likely involved in endocranial thermal regulation, infection, inflammation, and immune responses, and their distribution and prevalence can hence be of interest in human biology, evolutionary anthropology, and medicine.

Huge Pseudoaneurysm at the Aortic Bifurcation Misdiagnosed as a Mesenchymal Tumor: A Case Report.

Aortic pseudoaneurysms (PA) vary in size and may remain asymptomatic. PAs may be caused by vascular injury, such as trauma or surgery, or other non-traumatic causes, such as Bechet disease, infection, or penetrating atherosclerotic ulcers. The diagnosis of PAs may have been delayed for decades. We present a case of a PA detected incidentally in a male patient who experienced traumatic bowel perforation due to blunt abdominal trauma 30 years before presentation. Computed tomography (CT) displayed a 9.2 cm mass in the pelvis, initially considered a neoplasm of small bowel origin. Further analysis of the CT images suggested a thrombosed PA at the aortic bifurcation, which was confirmed via surgical exploration. Graft interposition was performed using a Dacron 16-8 mm graft and the patient recovered without any complications. This case highlights the importance of a high index of suspicion for the diagnosis of a thrombosed aortic PA.

Shaping the Neurovascular Unit Exploiting Human Brain Organoids.

Brain organoids, three-dimensional cell structures derived from pluripotent stem cells, closely mimic key aspects of the human brain in vitro, providing a powerful tool for studying neurodevelopment and disease. The neuroectodermal induction protocol employed for brain organoid generation primarily gives rise to the neural cellular component but lacks the vital vascular system, which is crucial for the brain functions by regulating differentiation, migration, and circuit formation, as well as delivering oxygen and nutrients. Many neurological diseases are caused by dysfunctions of cerebral microcirculation, making vascularization of human brain organoids an important tool for pathogenetic and translational research. Experimentally, the creation of vascularized brain organoids has primarily focused on the fusion of vascular and brain organoids, on organoid transplantation in vivo, and on the use of microfluidic devices to replicate the intricate microenvironment of the human brain in vitro. This review summarizes these efforts and highlights the importance of studying the neurovascular unit in a forward-looking perspective of leveraging their use for understanding and treating neurological disorders.

Management of lower extremity vascular injuries in pediatric trauma patients: 20-year experience at a level 1 trauma center.

Introduction: Pediatric lower extremity vascular injuries (LEVI) are rare but can result in significant morbidity. We aimed to describe our experience with these injuries, including associated injury patterns, diagnostic and therapeutic challenges, and outcomes. Methods: This was a retrospective review at a single level 1 trauma center from January 2000 to December 2019. Patients less than 18 years of age with LEVI were included. Demographics, injury patterns, clinical status at presentation, and intensive care unit (ICU) and hospital length of stay (LOS) were collected. Surgical data were extracted from patient charts. Results: 4,929 pediatric trauma patients presented during the 20-year period, of which 53 patients (1.1%) sustained LEVI. The mean age of patients was 15 years (range 1-17 years), the majority were Black (68%), male (96%), and most injuries were from a gunshot wound (62%). The median Glasgow Coma Scale score was 15, and the median Injury Severity Score was 12. The most commonly injured arteries were the superficial femoral artery (28%) and popliteal artery (28%). Hard signs of vascular injury were observed in 72% of patients and 87% required operative exploration. There were 36 arterial injuries, 36% of which were repaired with a reverse saphenous vein graft and 36% were repaired with polytetrafluoroethylene graft. One patient required amputation. Median ICU LOS was three days and median hospital LOS was 15 days. There were four mortalities. Conclusion: Pediatric LEVIs are rare and can result in significant morbidity. Surgical principles for pediatric vascular injuries are similar to those applied to adults, and this subset of patients can be safely managed in a tertiary specialized center. Level of evidence: Level IV, retrospective study.

The Role of the Vascular System in Degenerative Diseases: Mechanisms and Implications.

Degenerative diseases, encompassing a wide range of conditions affecting various organ systems, pose significant challenges to global healthcare systems. This comprehensive review explores the intricate interplay between the vascular system and degenerative diseases, shedding light on the underlying mechanisms and profound implications for disease progression and management. The pivotal role of the vascular system in maintaining tissue homeostasis is highlighted, as it serves as the conduit for oxygen, nutrients, and immune cells to vital organs and tissues. Due to the vital role of the vascular system in maintaining homeostasis, its dysfunction, characterized by impaired blood flow, endothelial dysfunction, and vascular inflammation, emerges as a common denominator of degenerative diseases across multiple systems. In the nervous system, we explored the influence of vascular factors on neurodegenerative diseases such as Alzheimer's and Parkinson's, emphasizing the critical role of cerebral blood flow regulation and the blood-brain barrier. Within the kidney system, the intricate relationship between vascular health and chronic kidney disease is scrutinized, unraveling the mechanisms by which hypertension and other vascular factors contribute to renal dysfunction. Throughout this review, we emphasize the clinical significance of understanding vascular involvement in degenerative diseases and potential therapeutic interventions targeting vascular health, highlighting emerging treatments and prevention strategies. In conclusion, a profound appreciation of the role of the vascular system in degenerative diseases is essential for advancing our understanding of degenerative disease pathogenesis and developing innovative approaches for prevention and treatment. This review provides a comprehensive foundation for researchers, clinicians, and policymakers seeking to address the intricate relationship between vascular health and degenerative diseases in pursuit of improved patient outcomes and enhanced public health.

Characteristics of the New Mast Cell-Rich Nodal Structure in the Rat Skin Surface.

Background: : Acupuncture, practiced for millennia, lacks a clear anatomical definition for acupoints. A prevailing theory suggests that acupoints overlap with skin areas with higher mast cell density. Skin spots stained with intravenously infused Evans blue (EB), indicative of neurogenic inflammation, have recently been posited as acupoints in rats. Objectives: : To demonstrate the concordance between EB-reactive skin spots and mast cell-enriched acupoints. Methods: : We employed staining and RNA-seq analysis to delineate the morphological characteristics and gene expression profiles of EB-reactive skin spots in rats. Results: : EB infusion revealed a novel nodal structure on the rat skin surface, visible to the naked eye, with dimensions of approximately 1 mm in both diameter and height. Around 30 such nodes were identified on one side of the abdominal area, spaced roughly 3 mm apart, excluding the linea alba. RNA-seq analysis indicated that the gene expression patterns within these nodes markedly differed from both non-nodal skin areas and lymph nodes. Histological examination using toluidine blue revealed a significantly greater mast cell count in the nodes than in non-nodal skin regions. Additionally, the nodes stained positively with Alcian blue and Hemacolor, reagents known to mark primo vascular tissues. Conclusion: : Our findings suggest that EB-reactive nodes are indeed rich in mast cells. Further research is warranted to establish these skin nodes as surface primo nodes.

Effects of Tumor Microenvironment on the Primo Vascular Pattern in the Mouse Model of Metastatic Breast Cancer.

Background: : Tumor survival, promotion, and metastatic functions are regulated by the tumor microenvironment (TME). The primo vascular system (PVS), the third circulatory system in animals, is currently thought to be a highly effective pathway for the spread of cancer cells. Objectives: : In the present study, we intend to determine the TME effects on the PVS pattern in breast cancer for the first time. Methods: : Heterotopic and orthotopic metastatic triple-negative breast cancer (TNBC) mice models were created. After 35 days, the skin was retracted, and a 2 cm skin incision was made up and down from the surface of the tumor tissue. In preparation for PVS staining, the dyes (trypan blue and alamarBlue) were injected throughout the tumor tissues. Under a stereomicroscope, PVS in heterotopic and orthotopic tumors was seen. Results: : According to our data, there are no appreciable variations in PVS patterns and density between heterotopic and orthotopic animal models. Furthermore, alamarBlue is a good option for tumor PVS staining, as demonstrated by our research. Conclusion: : For the first time, our data gave significant new information about the PVS in TNBC. Creating new anti-cancer treatments may be made possible by a better understanding of the biological characteristics of the TME and PVS.