Search Results (85)

Obstructive sleep apnea (OSA) is a common condition associated with intermittent hypoxia, systemic inflammation, and vascular dysfunction; mechanisms implicated in retinal disease pathogenesis. This real-world retrospective cohort study used data from the TriNetX Research Network to assess whether continuous positive airway pressure (CPAP) therapy reduces retinal disease incidence among adults with OSA and BMI between 25.0 and 30.0 kg/m². After 1:1 propensity score matching, 101,754 patients were included in the analysis. Retinal outcomes included diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal vein occlusion (RVO), and central serous chorioretinopathy (CSC). CPAP use was associated with a modest but statistically significant reduction in DR (3.2% vs. 3.4%, RR: 0.922, p = 0.016) and AMD (2.1% vs. 2.3%, RR: 0.906, p = 0.018), while no significant differences were found for RVO or CSC. These findings support prior evidence linking CPAP to improved retinal microvascular health and suggest a protective effect against specific retinal complications. Limitations include a lack of data on CPAP adherence, OSA severity, and imaging confirmation. Still, this study highlights the importance of interdisciplinary care between sleep and eye health, and the need for further prospective studies to validate CPAP’s role in preventing retinal disease progression in OSA patients. Full article

Background/Objectives: In septic shock, microcirculatory dysfunction contributes to organ failure and mortality. While sidestream dark-field (SDF) imaging is the reference method for assessing microvascular perfusion, its complexity limits routine use. This study evaluates near-infrared spectroscopy (NIRS) with vascular occlusion testing (VOT) as a potential bedside tool for monitoring microcirculatory changes following fluid resuscitation. Methods: Sixty-three fluid-responsive patients with sepsis were randomized to receive either 20% albumin or crystalloid. NIRS-VOT and sublingual SDF measurements were obtained at baseline and 60 min post-resuscitation. The reoxygenation slope (ReOx) derived from NIRS was calculated and compared with clinical severity scores and SDF-derived microcirculatory parameters. Results: ReOx significantly increased from baseline to 60 min in the albumin group (p = 0.025), but not in the crystalloid group. However, between-group differences at 60 min were not statistically significant. ReOx at 60 min was inversely correlated with APACHE II score (ρ = −0.325) and lactate (ρ = −0.277) and showed a weak inverse trend with norepinephrine dose. AUROC for ICU survival based on ReOx was 0.616. NIRS ReOx showed weak correlations with SDF parameters, including the number of crossings (p = 0.03) and the consensus proportion of perfused vessels (CPPV; p = 0.004). Conclusions: NIRS-VOT detected microcirculatory trends after albumin administration but showed limited agreement with SDF imaging. These findings suggest that NIRS and SDF assess different physiological domains. Further studies are warranted to define the clinical utility of NIRS as a microcirculation monitoring tool (Clinicaltrials.gov: NCT05357339). Full article

Background: Intercellular communication, facilitated by exosomes (Exos) derived from endothelial cells (ECs), significantly influences the regulation of angiogenesis. Leech extract significantly reduces ischemia–reperfusion injury, promotes angiogenesis, and improves neurological function in mice with stroke. However, further investigation is required to determine whether leech promotes angiogenesis through EC-Exo. Objective: This study aims to further explore whether leech regulates Exos to promote the establishment of collateral circulation in mice with ischemic stroke (IS) and the specific mechanisms involved. Methods: Here, we utilized an in vitro co-culture system comprising ECs and pericytes to investigate the impact of Leech-EC-Exo on enhancing the proliferation and migration of mouse brain microvascular pericytes (MBVPs). We further established an in vivo mouse model of middle cerebral artery occlusion/reperfusion (MCAO/R) to investigate the effects and underlying mechanisms of leech on collateral circulation establishment. Results: The findings demonstrated that leech significantly enhanced the in vitro cell migration number and migration number of pericytes. Therefore, it can also enhance the effect of EC-Exo on improving the infarct area and gait of mice, as well as modulating the HIFα-VEGF-DLL4-Notch1 signaling pathway to promote cerebral angiogenesis and facilitating the stable maturation of neovascularization in vivo. Conclusions: These results suggest that leech has the potential to enhance collateral circulation establishment, and its mechanism may involve the modulation of miRNA content in Exos and the promotion of signaling pathways associated with angiogenesis and vascular maturation. Full article

The rising incidence of colorectal cancer and ulcerative colitis underscores an urgent need for regenerative solutions to address functional deficits after colectomy. However, the creation of clinically applicable large intestine scaffolds remains underdeveloped. Here, we report the successful generation and thorough characterisation of transplantable-sized porcine large intestinal scaffolds via perfusion decellularisation. This method effectively preserved extracellular matrix (ECM) structural and biochemical integrity while minimising immunogenicity through cellular component removal. Crucially, native vasculature remained intact, confirmed by histology, DNA quantification, and high-resolution CT angiography. Despite efficient decellularisation, challenges including residual nucleic acids, ECM heterogeneity, and partial microvascular occlusion were noted, echoing ongoing limitations in engineered, perfusable, full-thickness scaffolds. In vivo implantation demonstrated favourable biocompatibility and host integration; however, thrombosis occurred due to the lack of pre-seeded cells, emphasising the necessity of recellularisation for functional perfusion prior to implantation. This study addresses significant field limitations, presenting the first reproducible approach for structurally intact, perfusable, full-thickness large intestinal scaffolds of transplantable dimensions. Our innovations offer a strong foundation for future integration of patient-derived cells, stem cells, and organoids, progressing toward clinically viable, scalable, tissue-engineered large intestine constructs, from xenogeneic sources, relevant for regenerative medicine, disease modelling, and pharmacological screening. Full article

Microcirculatory oscillations known as flowmotion are a recognized feature of blood flow that reflect the functional state of the vascular system. Many diseases are associated with impaired flowmotion, especially diseases that are accompanied by hypoxia. Low-frequency myogenic oscillations (0.052–0.15 Hz) are an important regulator of microvascular adaptation to hypoxia. Here, we study the myogenic component of flowmotion using the FMSF–PORH (Flow Mediated Skin Fluorescence–Post Occlusive Reactive Hyperemia) technique. Myogenic oscillations were strongly activated under hypoxic conditions caused by occlusion of the brachial artery or intermittent hypoxic treatment. A strong correlation was noted between the hypoxia sensitivity parameter HS (the intensity of myogenic oscillations activated by hypoxia) and the normoxic myogenic flowmotion parameter VM (the intensity of myogenic oscillations under normoxic conditions). If HS is considered as a direct measure of the microcirculation response to hypoxia, then VM can be considered a measure of the microcirculation’s readiness to provide this response. The predictive value of the VM parameter is presented. The assessment of myogenic activity under normoxia conditions could thus provide a simple and rapid diagnostic tool for health care practitioners. Full article

Background/Objectives: Microvascular plug embolization in the distal feeding artery (FA-MVP) and coil embolization targeting the nidus and feeding artery (NiFA-coil) are effective treatments for pulmonary arteriovenous malformations (PAVMs). This study compares their outcomes. Methods: A retrospective chart review was conducted on patients who underwent NiFA-coil or FA-MVP embolization for PAVMs between October 2014 and May 2024, with initial (short-term) follow-up chest CT imaging performed within 18 months, and the latest (long-term) follow-up performed at least 3 years post-treatment. Durable occlusion was defined as ≥70% shrinkage of the nidus or draining vein on follow-up CT. A Cox proportional hazards regression model assessed the association between technique and durable occlusion, with inverse propensity score weighting used to adjust for patient and PAVM characteristics. Results: A total of 142 PAVMs (48 FA-MVP, 94 NiFA-coil) in 85 patients were analyzed. Durable occlusion was 97.2% (138/142) at a median short-term follow-up of 4.2 months and 90.2% (37/41) at a median long-term follow-up of 56.0 months. Simple PAVMs were more frequent in the FA-MVP group (93.8%, 45/48) than in the NiFA-coil group (61.2%, 58/94) (p < 0.001). The NiFA-coil group had larger feeding arteries (3.8 mm vs. 2.3 mm, p < 0.001) and sac sizes (13.1 mm vs. 7.7 mm, p = 0.040). Short and long-term durable occlusion rates were comparable (NiFA-coil: 96.8% and 88.9%; FA-MVP: 97.8% and 92.9%, respectively; p > 0.99, p > 0.99). After propensity score matching, compared to FA-MVP, NiFA-coil had a hazard ratio for short-term persistence of 1.06 (95% CI, 0.16–6.99; p = 0.956). Conclusions: Both NiFA-coil and FA-MVP embolization are highly effective for PAVM treatment, with similar success rates. Full article

Acute chest syndrome (ACS) is among the most serious complications of sickle cell disease (SCD). While the pathogenesis of ACS is incompletely understood, endothelial damage and microvascular occlusion are critical components. Our previous studies have implicated small extracellular vesicles in the plasma of subjects with SCD in causing endothelial dysfunction. This suggested that microRNAs within these small EVs might be responsible for endothelial damage. The sequencing of microRNAs in small EVs from the plasma of subjects with SCD revealed that several miRNAs were differentially expressed between subjects with and without ACS history, including let-7c-5p. In a replication cohort, plasma let-7c-5p levels were quantified via RT-qPCR. The baseline plasma let-7c-5p level was twofold higher in patients without previous ACS. Furthermore, we observed a positive correlation between let-7c-5p levels and time to subsequent ACS events. These findings suggest a role for let-7c-5p in endothelial disruption underlying ACS pathogenesis. It may also serve as a novel biomarker for ACS detection and the prediction of disease progression. Full article

Background and Clinical Significance: Takotsubo cardiomyopathy (TCM), an acute stress-induced left ventricular dysfunction, stems from catecholaminergic surges leading to transient myocyte stunning, calcium overload, and microvascular dysregulation. Although most cases resolve spontaneously, roughly 10% deteriorate into fulminant cardiogenic shock, warranting mechanical circulatory support (MCS). Impella^® provides direct transvalvular LV unloading but carries elevated risks of hemolysis, vascular compromise, and thrombogenicity. Conversely, the intra-aortic balloon pump (IABP) enhances diastolic coronary perfusion and marginally reduces afterload via counterpulsation, albeit with less potent LV decompression. Optimal MCS selection in TCM-associated shock therefore hinges on balancing hemodynamic benefits against procedural morbidity. Case Presentation: A 72-year-old female with coronary artery disease, paroxysmal atrial fibrillation (status post–left atrial appendage occlusion), and stage 3 chronic kidney disease presented with anterior ST-segment elevations (V2–V4) and troponin I >1000 ng/L, progressing rapidly to cardiogenic shock and respiratory failure. Coronary angiography revealed mild luminal irregularities, while echocardiography demonstrated severely reduced ejection fraction (5–10%) with characteristic apical ballooning. Refractory elevations in pulmonary capillary wedge pressure, despite escalating inotropes and vasopressors, prompted IABP insertion for partial LV offloading. Over one week, her ejection fraction improved to 35%, facilitating weaning from pressor support, extubation, and discharge on guideline-directed medical therapy. Conclusions: In TCM complicated by shock, meticulous MCS selection is paramount. Although Impella confers more robust unloading, heightened device-related complications may be unjustified in a largely reversible disease. IABP can sufficiently stabilize hemodynamics, enable myocardial recovery, and mitigate morbidity, underscoring the importance of individualized decision-making in TCM-related shock. Importantly, no trial has shown that MCS confers a proven long-term mortality benefit beyond initial hemodynamic rescue. Full article

Good leptomeningeal collaterals (LMCs) after large vessel occlusion (LVO) extend the time window for endovascular therapy. The mechanisms regulating LMC activation are not fully understood. The aim of this study was to investigate the potential role of two vasoactive molecules endothelin-1 (ET-1)—a vasoconstrictor agent—and nitric oxide (NO)—a vasodilator agent—in the regulation of post-stroke LMCs. Ischemic stroke patients within 6 h of LVO were included. Collateral status was assessed using the Menon scoring system based on computed tomography angiography scans. Patients were accordingly divided into three groups: poor, intermediate, and good LMCs. Recanalization was evaluated using the modified thrombolysis in cerebral infarction (mTICI) score. Serum levels of ET-1 and NO were measured at three time points: T0 (<6 h), T1 (24 h), and T2 (48 h). A total of 105 patients were enrolled (mean age 76 ± 12.8 years): 44 with good (46.2%), 36 with intermediate (37.8%), and 22 with poor LMCs (23.1%). NO values decreased, whereas ET-1 values increased from T0 to T1 in all groups of patients. No significant association was found between serum ET-1 levels and collateral status. Higher ET-1 levels at T1 correlated with poor outcome regardless of the LMC status or the degree of recanalization (p = 0.030). A significant linear positive correlation was revealed at T0 between high levels of ET-1 and the neutrophil count (Spearman’s rho = 0.236, p = 0.035). Subgroup analysis showed a significant inverse correlation at T1 between NO and the collateral score (Spearman’s rho = −0.251, p = 0.021). Although we observed no significant association between LMC score and serum ET-1 concentrations, at 24 h higher ET-1 serum levels were predictive of poor outcome and higher NO levels were correlated with poor collateral status. These findings may indicate an inadequate microvascular reperfusion, possibly due to ET-1-mediated vasoconstriction, neutrophil activation, and NO-mediated oxidative stress, suggesting their potential role in the no-reflow phenomenon. Full article

Thrombotic microangiopathy (TMA) is a category of diseases consisting of thrombocytopenia, microangiopathic haemolytic anaemia, and widespread occlusive microvascular thrombosis. We report two cases of a thrombotic microangiopathic syndrome associated with non-invasive mucinous cysts and mucinous adenocarcinoma. TMA was treated in both cases by surgical removal of the tumours. We hypothesise that mucin secretion in the case of non-invasive mucinous cysts and paraneoplastic secretion of antibodies in the case of mucinous adenocarcinomas are the causes of endothelial damage with thrombocytopenia and microangiopathic haemolytic anaemia. Finally, patients with TMA who exhibit unusual clinical characteristics or weak responses to plasma exchange should be examined for an underlying tumour. Tumour treatment is the preferred therapy for tumour-associated TMA. Full article

Paracentral acute middle maculopathy (PAMM) is a macular condition primarily detected using optical coherence tomography (OCT) imaging. It presents as hyperreflective bands within the inner nuclear layer (INL) of the retina, often leading to localized degenerative phenomena. PAMM is a condition that reveals a dysfunction in the microvascular network of the retina. However, it is not an isolated phenomenon but rather an indicator of deeper and even systemic, prevalently vascular-related issues related to a wide array of conditions that impact circulation, including retinal vein and artery occlusion, diabetic retinopathy, and hypertensive retinal vascular changes. PAMM occurs due to impaired perfusion within the retinal deep capillary plexus, clinically leading to subtle but noticeable blind spots (scotomas) in the central visual field. Recent advances in imaging technology, particularly optical coherence tomography angiography (OCTA), have provided a clearer view of the underlying vascular alterations. Thus, PAMM may currently serve as a biomarker in broader ocular and systemic pathologies before disease progression. This review explores the latest reports in the literature on PAMM, from its characteristic imaging features to the evolving theories behind its development. By bridging the gap between ophthalmology and systemic health, PAMM may facilitate earlier diagnosis and tailored management strategies for conditions that extend far beyond the eye. Understanding this entity could ultimately transform our approach to assessing vascular health toward further research, risk prediction, and patient care. Full article

Background/Objectives: Patients with psoriasis exhibit endothelial dysfunction (EDy), which increases their cardiovascular risk. Excessive salt intake impairs endothelium-dependent vascular reactivity. However, research on EDy in psoriasis has focused primarily on larger vessels, leaving skin microcirculation unexplored. This study aimed to investigate the effects of a low-salt diet (LS diet, ~3.75 g/day) on microvascular reactivity in patients with chronic plaque psoriasis. Methods: Laser Doppler flowmetry was used to assess skin microcirculation blood flow in response to vascular occlusion (postocclusive reactive hyperemia, PORH), acetylcholine (acetylcholine-induced dilation, AChID), sodium nitroprusside (SNP-induced dilation, SNPID), and local heating (local thermal hyperemia, LTH). Blood and 24 h urine samples were collected for biochemical and inflammatory parameters and dietary adherence monitoring. Results: The results showed significant reductions in systolic (p = 0.021) and mean arterial blood pressure (p = 0.007) after the LS diet. AChID increased by 16% (p = 0.029) regardless of blood pressure changes, especially in normolipemic, normotensive patients without excess visceral fat. Importantly, significant sex differences were observed, with significant improvement in endothelial function observed only in women (p = 0.031 vs. p = 0.477). PORH did not change significantly; however, a Fourier transformation analysis revealed that the endothelial component of the PORH was significantly improved following the LS diet protocol. The duration of psoriasis negatively correlated with changes in AChID (R = −0.46, p = 0.036) and LTH (R = −0.45, p = 0.041) after the LS diet, indicating that prolonged low-grade inflammation reduced endothelial function reversibility. Additionally, lower triglyceride, uric acid, and BMI levels were significant predictors of better endothelial function improvement following the LS diet. Conclusions: This study supports the beneficial effect of the early introduction of an LS diet in the treatment protocols for patients with psoriasis. Full article

Background/Objectives: Hemorrhagic transformation after endovascular thrombectomy predicts poor outcomes in acute ischemic stroke with large-vessel occlusion. The roles of microRNAs (miRNAs) in the pathogenesis of parenchymal hematoma (PH) after endovascular thrombectomy still remain unclear. This study aimed to investigate the miRNA and mRNA regulatory network associated with PH after mechanical reperfusion in an animal stroke model and an oxygen–glucose deprivation/reoxygenation (OGD/R) model. Methods: Twenty-five miRNAs were assessed in a mechanical reperfusion-induced hemorrhage transformation model in rats under hyperglycemic conditions receiving 5 h middle cerebral artery occlusion. The differentially expressed miRNAs associated with PH were assessed in a neuron, astrocyte, microglia, brain microvascular endothelial cell (BMEC), and pericyte model of OGD/R. The predicted target genes of the differentially expressed miRNAs were further assessed in the animal model. The miRNA-mRNA regulatory network of PH was established. Results: Thirteen down-regulated miRNAs (miRNA-29a-5p, miRNA-29c-3p, miRNA-126a-5p, miRNA-132-3p, miRNA-136-3p, miRNA-142-3p, miRNA-153-5p, miRNA-218a-5p, miRNA-219a-2-3p, miRNA-369-5p, miRNA-376a-5p, miRNA-376b-5p, and miRNA-383-5p) and one up-regulated miRNA (miRNA-195-3p) were found in the rat peri-infarct with PH after mechanical reperfusion. Of these 14 PH-related miRNAs, 10 were significantly differentially expressed in at least two of the five neuron, astrocyte, microglia, BMEC, and pericyte models after OGD/R, consistent with the animal stroke model results. Thirty-one predicted hub target genes were significantly differentially expressed in the rat peri-infarct with PH after mechanical reperfusion. Forty-nine miRNA-mRNA regulatory axes of PH were revealed, and they were related to the mechanisms of inflammation, immunity, oxidative stress, and apoptosis. Conclusions: Fourteen miRNAs were associated with PH after mechanical reperfusion in the rat stroke and the OGD/R models. Simultaneously differentially expressed miRNAs and related genes in several cells of the neurovascular unit may serve as valuable targets for PH after endovascular thrombectomy in acute ischemic stroke. Full article

Background/Objectives: To investigate the potential association between the endothelial dysfunction and arterial stiffness with retinal changes observed through optical coherence tomography (OCT) and OCT-angiography (OCT-A) in patients with retinal vein occlusion (RVO). Methods: Participants in this cross-sectional study were 28 patients with RVO. The demographic and clinical characteristics of all participants were recorded. Comprehensive ophthalmologic examinations were performed, including fundus photography, OCT and OCT-A. Endothelial dysfunction was assessed by measuring the endothelial glycocalyx thickness via the perfused boundary region (PBR5-25). Arterial stiffness was evaluated by measuring the carotid-femoral pulse wave velocity (PWV), the central systolic and diastolic blood pressures (cSBP and cDBP) and the augmentation index (Aix). For each ophthalmological outcome, we generated a saturated linear regression model with demographic and systemic vascular parameters serving as independent variables. Regression coefficients with the corresponding 95% confidence intervals (CIs) were reported. A p value < 0.05 was considered as statistically significant. Results: A 1 m/s increase in PWV was associated with a 0.6% reduction in inferior macular vessel density (VD) (p = 0.050). A 10 mmHg increase in cSBP was associated with a 0.03 mm² increase in foveal avascular zone (FAZ) area (p = 0.033). A 1% increase in Aix was associated with a 0.005 mm² increase in FAZ area (p = 0.008). A 1 μm increase in PBR5-25 was associated, on average, with a 4.4% decrease in superior peripapillary VD (p = 0.027). Conclusions: In patients with RVO, structural and microvascular retinal parameters were significantly associated with markers of endothelial dysfunction and arterial stiffness. Full article

Introduction: We sought to determine by systematic review the independent effect of overweight/obesity on cutaneous microvascular reactivity in adults as measured by laser-Doppler fluxmetry. Methods: CINAHL Complete, SPORTSDiscus, Embase, Medline, and Cochrane Library were searched until March 2024 to identify studies investigating cutaneous microvascular reactivity in an overweight/obese but otherwise healthy group versus a lean/healthy weight. Reporting is consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Quality appraisal of included studies was performed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. Results: Nineteen eligible articles reported on 1847 participants. Most articles reported impaired cutaneous microvascular reactivity in cohorts with overweight/obesity compared to cohorts with lean/healthy weight. Investigating reactivity via post-occlusive reactive hyperaemia (PORH) and iontophoresis of acetylcholine (ACh) has shown significance. No significant differences were reported between groups in response to local heating or to iontophoresis of methacholine or insulin, while findings of the effect of obesity on iontophoresis of sodium nitroprusside (SNP) were mixed. Conclusions: The pathophysiology of impaired cutaneous microvascular reactivity in overweight/obesity requires further investigation; however, impaired function of vasoactive substances, endothelial dysfunction, sensory nerves, and calcium-activated potassium channels may be implicated. Identifying these impaired microvascular responses should inform possible therapy targets in overweight and obesity.activated potassium channels may be implicated. Identifying these impaired microvascular responses should inform possible therapy targets in overweight and obesity. Full article