Search Results (425)

Diabetes-related pathophysiological processes contribute to endothelial dysfunction, arterial stiffening (AS), hypertension, vascular remodeling, and impaired myocardial perfusion. This study aimed to assess the relationship between arterial wall parameters and sST2 concentration as potential risk factors in type 2 diabetes (T2DM) and investigate sex-related differences. To achieve this, we enrolled 100 patients with suspected or exacerbated coronary artery disease (CAD) and divided them into a T2DM group (n = 58) and a control group (n = 42). Endothelial reactivity (lnRHI), ABI, sST2 levels, and carotid–femoral (cfPWV) and carotid–radial pulse wave velocity (crPWV) were assessed. Coronary angiography was performed in every patient, and epicardial flow and myocardial perfusion were evaluated using QuBE and FLASH. Our results showed that the coronary angiographic findings were similar in both groups. However, T2DM patients had a significantly higher central AS (cfPWV 10.8 ± 2 vs. 9.9 ± 2.7 m/s, p < 0.05) and vascular age (70.0 ± 12.3 vs. 61.3 ± 15.4 years, p < 0.05), while peripheral AS, RHI, and ABI showed no differences. CfPWV correlated with renal function; higher HbA1c and sST2 levels were additionally associated with advanced vascular age. Notably, central AS and vascular age were higher in men with T2DM but not in women. These findings indicate that T2DM patients exhibit increased central AS and vascular aging, influenced by sST2 levels, suggesting fibrosis as a target for precision medicine in T2DM. Full article

The impact of Oedema Disease produced by Shiga toxigenic Escherichia coli (STEC) in swine is increasing in some production countries due to increasing limitations on treatment with antimicrobials and zinc oxide, either because of the increased prevalence of multi-resistant strains or because of legal restrictions. The main pathological effect of Shiga toxin 2e is represented by damage to the endothelial cells of the blood vessel walls, leading to liquid extravasation and oedema formation in multiple tissues. These oedemas are generally easily identifiable in acute clinical cases. However, disease caused by Shiga toxin can occur without any externally visible oedema in the pigs, as observed in the subclinical presentation of Oedema Disease. It also causes productive losses, so it is important to identify and/or diagnose cases to set up control measures in order to optimize production and health. This article includes a comprehensive review of lesions and signs caused by Shiga toxin toxicosis in pigs, as well as other insights about the aetiology and epidemiology of STEC in pigs, and the effect of Shiga toxin recombinant toxoid vaccines in reducing these clinical and subclinical signs under field conditions. Full article

Background: Cerebral aneurysm (CA) is a focal or diffuse pathological dilation of the cerebral arterial wall that arises due to various etiological factors. It represents a serious vascular condition, particularly affecting the elderly, and carries a high risk of rupture and neurological morbidity. Clonidine (CL), an α2-adrenergic receptor agonist, has been reported to suppress aneurysm progression; however, its underlying molecular mechanisms, especially in relation to cerebral endothelial dysfunction, remain unclear. This study aimed to investigate the potential of CL to mitigate CA development by modulating apoptosis, inflammation, and oxidative stress in an Angiotensin II (Ang II)-induced endothelial injury model. Methods: Human brain microvascular endothelial cells (HBMECs) were used to establish an in vitro model of endothelial dysfunction by treating cells with 1 µM Ang II for 48 h. CL was administered 2 h prior to Ang II exposure at concentrations of 0.1, 1, and 10 µM. Cell viability was assessed using the MTT assay. Oxidative stress markers, including reactive oxygen species (ROS) and Nitric Oxide (NO), were measured using 2′,7′–dichlorofluorescin diacetate (DCFDA). Gene expression levels of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP-2 and MMP-9), high mobility group box 1 (HMGB1), and nuclear factor kappa B (NF-κB) were quantified using RT-qPCR. Levels of proinflammatory cytokines; tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and interferon-gamma (IFN-γ); were measured using commercial ELISA kits. Results: Ang II significantly increased ROS production and reduced NO levels, accompanied by heightened proinflammatory cytokine release and endothelial dysfunction. MTT assay revealed a marked decrease in cell viability following Ang II treatment (34.18%), whereas CL preserved cell viability in a concentration-dependent manner: 44.24% at 0.1 µM, 66.56% at 1 µM, and 81.74% at 10 µM. CL treatment also significantly attenuated ROS generation and inflammatory cytokine levels (p < 0.05). Furthermore, the expression of VEGF, HMGB1, NF-κB, MMP-2, and MMP-9 was significantly downregulated in response to CL. Conclusions: CL exerts a protective effect on endothelial cells by reducing oxidative stress and suppressing proinflammatory signaling pathways in Ang II-induced injury. These results support the potential of CL to mitigate endothelial injury in vitro, though further in vivo studies are required to confirm its translational relevance. Full article

Microfluidic methods are an important tool for studying the microrheology of blood and the mechanical properties of blood cells—erythrocytes, leukocytes, and platelets. In patients with diabetes, hypertension, obesity, sickle cell anemia, or cerebrovascular or peripheral vascular diseases, hemorheological alterations are commonly observed. These include increased blood viscosity and red blood cell (RBC) aggregation, along with reduced RBC deformability. Such disturbances significantly contribute to impaired microcirculation and microvascular perfusion. In blood vessels, abnormal hemorheological parameters can elevate resistance to blood flow, exert greater mechanical stress on the endothelial wall, and lead to microvascular complications. Among these parameters, erythrocyte deformability is a potential biomarker for diseases including diabetes, malaria, and cancer. This review highlights recent advances in microfluidic technologies for in vitro assays of RBC deformability and aggregation, as well as leukocyte aggregation and adhesion. It summarizes the core principles of microfluidic platforms and the experimental findings related to hemodynamic parameters. The advantages and limitations of each technique are discussed, and future directions for improving these devices are explored. Additionally, some aspects of the modeling of the microrheological properties of blood cells are considered. Overall, the described microfluidic systems represent promising tools for investigating erythrocyte mechanics and leukocyte behavior. Full article

A considerable amount of scientific evidence demonstrates that the regime of magnitude, direction, and/or frequency of wall shear stress (WSS) modulates endothelial cell function and structure, influencing vascular biology in health and disease. Advances in computational fluid dynamics (CFD) and fluid–structure interaction (FSI) simulations in cardiovascular medicine have enabled accurate WSS quantification, correlating flow behavior and its interaction with the vessel wall with disease progression. To effectively analyze and interpret the results of numerical simulations, various descriptors of blood flow were defined. Such indicators allow researchers to quantify and characterize key aspects of blood flow, facilitating the study of healthy and pathological conditions, medical device design, and treatment planning. However, a very fast-growing collection of hemodynamic metrics were defined and used: whether called indicators, parameters, metrics, or indexes, they will be here referred to as hemodynamic descriptors. This narrative review was aimed at synthesizing scientific literature about the descriptors used to analyze blood flow in computational cardiovascular studies, highlighting their significance, applications, and advancements. Full article

Background and Aim: Syphilis, caused by Treponema pallidum, classically presents with genital or anal chancres; rectal involvement is rare and frequently misdiagnosed as inflammatory bowel disease or malignancy. We describe an unusually severe case of syphilitic proctitis in the setting of advanced HIV-related immunosuppression (CD4 39 cells/µL), in which targeted immunophenotyping (ERG and CD38) was a valuable adjunctive tool in the differential diagnosis. Case Presentation: A 46-year-old man with a recent history of erosive gastritis and esophageal candidiasis presented after six months of unintentional 20 kg weight loss, profound fatigue, intermittent fevers, profuse diarrhea, and two episodes of hematemesis. Workup revealed a new diagnosis of HIV infection (CD4: 39 cells/µL; viral load: 87,837 copies/mL). Contrast-enhanced CT demonstrated uniform, concentric rectal wall thickening (“target sign”). Colonoscopic biopsy showed exuberant granulation tissue and dense plasma cell infiltrates. Immunohistochemistry revealed a dense infiltrate of CD38-positive plasma cells and ERG-positive endothelial proliferation. These findings, in the context of positive serology, were highly supportive of a spirochetal etiology and helped differentiate it from potential mimics. Serology was positive for latent late syphilis (VDRL 1:64). The patient received three weekly doses of intramuscular benzathine penicillin; lumbar puncture excluded neurosyphilis. Discussion: This is among the first reported cases of syphilitic proctitis in a patient with CD4 < 50 cells/µL, where advanced immunophenotyping differentiated syphilitic inflammation from neoplastic or inflammatory mimics. Profound immunosuppression accelerates disease progression and yields atypical clinical features. Conclusion: In HIV-infected patients with chronic rectal symptoms, especially those with CD4 < 50 cells/µL, syphilitic proctitis must be considered. Integration of radiologic assessment, histopathology with ERG/CD38 staining, and serologic testing permits prompt diagnosis. Early benzathine penicillin therapy and rigorous clinical and serologic follow-up are essential to prevent complications, including neurosyphilis. Full article

Atherosclerosis (AS), a progressive inflammatory disease of coronary arteries, the aorta, and the internal carotid artery, is considered one of the main contributors to cardiovascular disorders. Blood flow is restricted by accumulating lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the intima of arterial walls. Butyrate maintains gut barrier integrity and modulates immune responses. Butyrate regulates G-protein-coupled receptor (GPCR) signaling and activates nuclear factor kappa-B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factors (IFRs) involved in the production of proinflammatory cytokines. Depending on the inflammatory stimuli, butyrate may also inactivate NF-κB, resulting in the suppression of proinflammatory cytokines and the stimulation of anti-inflammatory cytokines. Butyrate modulates mitogen-activated protein kinase (MAPK) to promote or suppress macrophage inflammation, muscle cell growth, apoptosis, and the uptake of oxidized low-density lipoprotein (ox-LDL) in macrophages. Activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway plays a role in lipid metabolism, inflammation, and cell differentiation. Butyrate inhibits interferon γ (IFN-γ) signaling and suppresses NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) involved in inflammation and scar tissue formation. The dual role of butyrate in AS is discussed by addressing the interactions between butyrate, intestinal epithelial cells (IECs), endothelial cells (ECs) of the main arteries, and immune cells. Signals generated from these interactions may be applied in the diagnosis and intervention of AS. Reporters to detect early AS is suggested. This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article

Background/Objectives: Apolipoprotein E receptor-2 (apoER2) exists in various alternatively spliced forms, including variants that express apoER2 with or without exon 19 in the cytoplasmic domain. This study compared vascular response to endothelial denudation, as well as diet-induced atherosclerotic and metabolic diseases, between genetically modified mice that exclusively expressed the apoER2 splice variant with or without exon 19 to determine the impact of apoER2 exon 19 motif in cardiometabolic disease modulation. Methods: Vascular response to injury was assessed by measuring neointima area of the carotid arteries after endothelial denudation. The genetically modified mice were also fed a high-fat high-cholesterol diet for 16 weeks for the determination of body weight gain, glucose and insulin levels, glucose tolerance and insulin secretion. Additionally, adipose tissue inflammation was assessed by analysis of adipose gene expression, and atherosclerosis was characterized by measuring fatty lesion size in the whole aorta, as well as in the aortic roots. Results: The results showed that whereas the expression of either splice variant is sufficient to impede denudation-induced fibrotic neointima formation and complex necrotic atherosclerotic lesions, the expression of the apoER2 splice variant containing exon 19 is necessary for the complete protection of injury-induced neointima formation in the vessel wall. However, exclusive expression of either apoER2 cytoplasmic splice variant does not influence the early phase of atherogenesis. Additionally, the exclusive expression of apoER2 without exon 19 promotes adipocyte inflammation and accelerates diet-induced insulin resistance and glucose intolerance. Conclusions: These results indicate that the apoER2 cytoplasmic variants have distinct and cell type-specific roles in influencing cardiometabolic disease development. Full article

Endothelial dysfunction appears early in type 1 diabetes (T1D). The detection of the first vascular disturbances in T1D patients is crucial, and the introduction of novel techniques, such as flow-mediated skin fluorescence (FMSF) and adaptive optics retinal camera (Rtx) imaging, gives hope for better detection and prevention of angiopathies in the future. In this study, we aimed to investigate microcirculation disturbances in pediatric patients with T1D with the use of FMSF and Rtx imaging. This research focused especially on the relationship between microvascular parameters obtained in FMSF and Rtx measurements, and the glycemic control evaluated in continuous glucose monitoring (CGM) reports. We observed significantly increased wall thickness (WT) and wall-to-lumen ratio (WLR) values in T1D patients in comparison to the control group. Although we did not observe significant differences between the T1D and control groups in the FMSF results, a trend toward significance between the time in range (TIR) and hyperemic response (HR_max) and an interesting correlation between the carotid intima-media thickness (cIMT_max) and HR_max. were observed. In conclusion, FMSF and Rtx measurments are innovative techniques enabling the detection of early microvascular disturbances. Full article

Introduction: Angiosarcomas arise from vascular or lymphatic endothelial cells and can develop at any site. Visceral angiosarcomas are aggressive high-grade tumors with a high risk of recurrence, metastasis, and poor survival. Nationwide studies with long-term follow-up are limited, but crucial for understanding this malignancy. This study aimed to describe a national cohort of patients with visceral angiosarcomas and estimate long-term survival, local recurrence, and metastases. Methods: We included all adult patients in Denmark diagnosed with histologically confirmed visceral angiosarcoma from 2000 to 2017. Data were obtained from the Danish Pathology Register and the Danish Sarcoma Database, both providing nationwide and comprehensive records. Additional information on demographics, comorbidities, symptoms, diagnosis, tumor location, treatment, recurrence, and survival were collected from registries and health records. Results: Eighteen patients with visceral angiosarcoma were identified, corresponding to an incidence of one per 5.5 million inhabitants per year. The median age was 56.5 years (IQR: 50–70), and 56% were female. Tumors were most commonly located in the kidney, liver, and thoracic wall. Metastases were present at diagnosis in 17% and developed later in 50%. Surgery was performed in 61%, with R0 resection in 55%. Median overall survival was 249 days (IQR: 121–858), and the 5-year survival rate was 11%. Only one patient (6%) remained alive at long-term follow-up. Conclusions: This Danish nationwide study confirms that visceral angiosarcomas are rare, highly aggressive tumors with a poor prognosis, consistent with international findings. Despite the small cohort, the disease demonstrated significant heterogeneity in anatomical location, metastatic pattern, and treatment approaches. Full article

Background/Objectives: Bovine pericardial valve conduits (PVCs) are commonly used for right ventricular outflow tract reconstruction in both pediatric and adult patients. Calcification, particularly prevalent in children and young adults, is a leading cause of conduit failure and is affected by the chemical composition of the treated biomaterials. In this study, we aimed to compare the structural changes in diepoxy-treated (DE-PVCs) and glutaraldehyde-treated PVCs (GA-PVCs) and to identify factors contributing to tissue mineralization in a large animal model. Methods: Pulmonary artery replacement was performed in minipigs (33–88 kg) using twelve DE-PVCs and four GA-PVCs. After six months, the animals were euthanized, and the explanted PVCs underwent macroscopic and microscopic examination. Results: Large calcium deposits formed along conduit joining suture (CJS) lines in all PVCs, regardless of the cross-linking agent. Mineral clusters surrounded the multifilament braided thread, and its fibers were encrusted with hydroxyapatite crystals. In DE-PVCs, no mineralization occurred outside the suture lines, and they showed successful integration and graft vitalization with a uniform neointima and well-developed endothelial monolayer. GA-PVCs developed a rigid external capsule, foci of collagen fiber calcification within the walls, and neointimal hyperplasia with limited endothelial coverage. Conclusions: In PVCs, calcification predominantly occurs along the CJS lines, where the multifilament suture acts as a nucleation site for hydroxyapatite crystals. DE treatment prevents collagen mineralization, unlike GA, and offers better integration, reduced neointimal hyperplasia, and a well-developed endothelial layer. These findings suggest that DE-PVCs may be a superior option for pediatric cardiac surgery by reducing calcification and improving conduit durability. Overall, the results will help optimize PVC manufacturing strategies to lower the risk of conduit failure. Full article

Nitric oxide (NO) is a well-known member of the reactive oxygen species (ROS) family. The extent of its concentration influences whether it produces beneficial physiological effects or harmful toxic reactions. In a blood system, NO is generally produced by nitric oxide synthase (NOS) in the endothelium. Then, it diffuses into the smooth muscle wall causing a vasodilatation, and it can also be diluted in a lumen blood stream. In the present study, we analyzed a convectional reaction–diffusion of NO in a 3D digital phantom of a short segment of small arteries. NO concentrations were analyzed by applying numerical solutions to the boundary problems, which included the Navier–Stokes equation, Darcy’s law, varying consumption of NO, and the dependence of NOS activity on shear stress. All the boundary problems were evaluated using COMSOL Multiphysics software ver. 5.5. The role of two diffusive barriers surrounding the endothelium producing NO was theoretically proven. When the eNOS rate remains unchanged, an increase in the fenestration of the internal elastic lamina (IEL) and a decrease in the diffusive permeability of a thin layer of endothelial surface glycocalyx (ESG) lead to a notable rise in the NO concentration in the vascular wall. The alterations in pore count in IEL and the viscosity of ESG are considered to be involved in the physiological and pathological regulation of NO concentrations. Full article

Ventricular chamber development involves the coordinated maturation of diverse cardiomyocyte cell populations. In the human fetal heart, single-cell and single-nucleus RNA sequencing technologies and spatial transcriptomics reveal marked regional gene expression differences. In contrast, the mouse ventricular wall appears more homogeneous, except for a transient hybrid cardiomyocyte population co-expressing compact (Hey2) and trabecular (Irx3, Nppa, Bmp10) markers, indicating a transitional lineage state. To further investigate this, we used in situ hybridization (ISH) to examine the expression of a selected set of cardiomyocyte markers in normal and left ventricular non-compaction cardiomyopathy (LVNC) mouse models. In developing mouse ventricles, the expression of key marker genes was largely restricted to two wide myocardial domains, compact and trabecular myocardium, suggesting a less complex regional organization than the human fetal heart. Other markers labeled endocardial and coronary endothelial cells rather than cardiomyocytes, differing from patterns observed in the human heart. In the LVNC model, various markers exhibited altered spatial expression, indicating that the precise regional organization of gene expression is critical for normal ventricular wall maturation. These findings underscore the critical role of spatially regulated gene programs in ventricular chamber development and point to their potential involvement in cardiomyopathy pathogenesis. Full article

Endothelial dysfunction (ED) has been identified as a precursor to micro- and macroangiopathic complications and an independent risk factor for major adverse cardiac events (MACEs). Recent studies have identified a novel risk factor for ED: severe aortic stenosis (AS). Traditionally linked to other established risk factors for endothelial cell dysregulation, AS has emerged as a contributor to ED, which is supported by the improvement of endothelial function following transcatheter (TAVR) or surgical (SAVR) interventions. Furthermore, the observation of ED in patients with a dysfunctional bicuspid aortic valve (BAV) at a younger age suggests a distinct impact of AS on ED. A promising hypothesis is a hemodynamic theory suggesting that changes in the shear stress of the ascending aortic wall and peripheral vessels, along with subclinical hemolysis caused by turbulent blood flow, could lead to reduced nitric oxide (NO) bioavailability. Current hypotheses on ED have yet to consider the influence of concomitant aortic stenosis in BAV. Additionally, studies examining potential intravascular hemolysis in BAV patients or the impact of surgical treatment of this defect on endothelial function are scarce. The aim of this review is to summarize the current knowledge on the mechanisms underlying ED in patients with AS or BAV and to identify possible directions for future research. Full article

Background: High-intensity intermittent training (HIIT) has been proven to improve cardio-metabolic and respiratory health outcomes. In addition, 20-hydroxyecdysone from plant extracts has been studied for its anabolic effects. However, studies examining these two interventions in individuals who are obese or overweight are limited. This study, thus, examined the effects of HIIT combined with Asparagus officinalis (A. officinalis) extract supplementation on cardiovascular and pulmonary function parameters in obese and overweight individuals. Methods: Seventy-two obese and overweight participants were randomized into four groups (n = 18 each): the control (CON) group; HIIT group (HIIT for 3 days/week); AOE (A. officinalis extract) group (supplementation with 20E at 1.71 mg/kg/day); and HIIT + AOE group. Pre- and 12-week post-intervention measures included heart rate (HR), HR variability, endothelial function, blood pressure (BP), BP variability, pulmonary function and volume, respiratory muscle strength, chest expansion, and body composition. Results: The HIIT + AOE group showed better HR variability with higher high-frequency power and a lower low-frequency/high-frequency ratio (both p = 0.038) compared to the CON group. The peak blood flow increased in both the HIIT (p = 0.03) and HIIT + AOE (p = 0.028) groups, but only the HIIT group had a shorter vascular recovery time (p = 0.048). The maximum expiratory pressure was increased in both the HIIT and HIIT + AOE groups compared to the CON group (p = 0.029 and p = 0.041). The ratio of forced expiratory volume in one second to forced vital capacity, the percent-predicted FEV₁/FVC, and chest wall expansion were higher in the HIIT + AOE group than in the CON group (p = 0.047, p = 0.038, and p = 0.001). The waist-to-hip ratio was lower in the HIIT + AOE group than in the CON group (p = 0.043). There were no significant differences in HR, BP, BP variability, or pulmonary volume parameters among groups. Conclusions: The combination of HIIT with A. officinalis extract supplementation markedly improves HR variability. Moreover, it also greatly improves expiratory muscle strength, chest wall expansion, pulmonary function, and body composition parameters in obese and overweight individuals. Full article