Alterations Of Vessels Research Articles

Intra-cisterna-magna bevacizumab injection (ICM-BI) reproduces pathological alterations of cerebral small vessel diseases.

General modeling strategies for sporadic cerebral small blood vessel diseases (CSVDs) include limiting blood stream in large blood vessels and inducing systemic hypertension, in which small blood vessel deficit is either a secondary or concomitant pathology. In the current study, we introduce that intra-cisterna-magna Bevacizumab injection (ICM-BI) directly causes cerebral small blood vessel injury by neutralizing VEGF-A, the indispensable growth factor for angiogenesis. ICM-BI reproduces neuro-functional impairment, tight junction loss, cerebral micro-bleeds (CMBs), amyloid peptide accumulation, neuronal injury, white matter loss, and glial cell activation, which are common manifestations of sporadic CSVDs. Compared with existing CSVD models, small blood vessel injury is more prominent in the ICM-BI brain. Moreover, no significant alteration in large blood vessels or peripheral organs after ICM-BI is recorded. We thus propose that ICM-BI is a neat, economic and applicable methodology to establish murine sporadic CSVD model.

In-depth cerebrovascular lipidomics profiling for discovering novel biomarkers and mechanisms in moyamoya and intracranial atherosclerotic disease.

Despite considerable research efforts, the precise etiology and underlying pathways contributing to Moyamoya Disease (MMD) remain poorly understood. Moreover, the overlapping vascular pathologies shared between MMD and Intracranial Atherosclerotic Disease (ICAD) pose challenges in clinical differentiation, even with gold-standard cerebral angiography. An in-depth exploration of lipidomic alterations in cerebral intracranial MMD vessels could offer valuable insights into the pathogenesis of MMD-related mechanisms, encompassing MMD and ICAD, and unveil novel biomarkers and potential therapeutic targets. However, to date, comprehensive lipidomic profiling has been lacking. To discover novel biomarkers and unravel the pathophysiological mechanisms underlying MMD, we conducted a lipidomics analysis to characterize various lipid species in matched human extracranial and intracranial artery tissues from patients diagnosed with MMD (n=99) and ICAD (n=12). Our analysis identified 569 lipid species and delineated a robust panel of lipidomic biomarkers capable of effectively distinguishing MMD from ICAD (area under curve=0.98), as determined by receiver operating characteristic curve analysis. Notably, we observed a significantly more pronounced positive correlation of diacylglycerols and a negative association of triglycerides in intracranial artery tissues of MMD patients compared to those with ICAD, suggesting a potential role of dysregulated diacylglycerol-induced signaling in MMD pathogenesis. Furthermore, our investigation into the correlations of critical differential intracranial artery vessel lipid species between MMD and ICAD and clinical parameters revealed negative associations with plasma iron levels, implying a potential link between plasma iron metabolism and artery lipid homeostasis during MMD pathogenesis. These findings offer promising prospects for advancing clinical diagnosis for enhanced differentiation between the two disease conditions. Additionally, they shed light on the fundamental mechanisms implicated in MMD pathogenesis and suggest potential therapeutic avenues through targeting artery vessel lipids or plasma iron levels.

Retinal microvascular changes in patients with pancreatitis and their clinical significance

Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1–C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.

Brain ischemia causes systemic Notch1 activity in endothelial cells to drive atherosclerosis

Stroke leads to persistently high risk for recurrent vascular events caused by systemic atheroprogression that is driven by endothelial cell (EC) activation. However, whether and how stroke induces sustained pro-inflammatory and proatherogenic endothelial alterations in systemic vessels remain poorly understood. We showed that brain ischemia induces persistent activation, the upregulation of adhesion molecule VCAM1, and increased senescence in peripheral ECs until 4weeks after stroke onset. This aberrant EC activity resulted from sustained Notch1 signaling, which was triggered by increased circulating Notch1 ligands DLL1 and Jagged1 after stroke in mice and humans. Consequently, this led to increased myeloid cell adhesion and atheroprogression by generating a senescent, pro-inflammatory endothelium. Notch1- or VCAM1-blocking antibodies and the genetic ablation of endothelial Notch1 reduced atheroprogression after stroke. Our findings revealed a systemic machinery that induces the persistent activation of peripheral ECs after stroke, which paves the way for therapeutic interventions or the prevention of recurrent vascular events following stroke.

Changes in Blood Vessel Morphology in Erythematous Skin of Atopic Dermatitis Patients

Background: Atopic dermatitis is an inflammatory skin disease characterized by erythematous changes and abnormalities in microvasculature. Regarding the research questions, this cross-sectional study conducted from January 5 to July 5, 2019 at Watim Medical and Dental College, Rawat and the findings on observed vascular alterations supposed to present the mean age, standard deviation and p-value as follows: Objectives: , the morphology of the blood vessels in the erythematous skin of the patients with AD and controls matched based on their age will be examined. Study Design: A Cross-sectional study. Place and Duration of Study: from 05-Jan-2019 to 05-Jan-2020 in the Department Pathology, Watim Medical and Dental College Rawat, Pakistan. Methods: This descriptive cross sectional study recruited the patients from the Department of Pathology, Watim Medical and Dental College, Rawat over a period of six months from January 5, 2019 to July 5, 2019. Adult patients, comprising 100 in number, diagnosed to have atopic dermatitis were used in the study. The patient ages were noted down and dermoscopy of the morphological changes occurring in the blood vessels at erythematous lesions were observed. Descriptive statistics were used in a bid to calculate mean age, standard deviation as well as the p-value. This research study was reviewed and cleared by the Institution’s ethical committee before its conduct. Results: Patients 100 Patients were selected for the study, Moreover the patients diagnosed with atopic dermatitis were between the age group of 18-65 years with mean age of 35. 4 years (SD 12. 7), refer to the table 1. Morphological assessment of blood vessels in erythematous skin showed that 60% of the patients were having abnormal morphological pattern whereas 40% of patients demonstrated normal morphology (table 2). Co-relating and comparing the normal and altered Vascular architecture mathematical statistics revealed the fact with P-values equal to 0. 045 (Table 4). The findings of increased vascular alterations in lesions of atopic dermatitis evident from the results in Table 5 indicate that blood vessel alterations are associated with the severity of skin condition rashes. Conclusion: our study identify that extensive vascular changes at the skin of those with atopic dermatitis while stressing on the importance of these changes in disease progression. Targeted therapies for the aforementioned vascular changes could be promising in the future as compared to the ones that address mere clinical manifestations. Keywords: AMD, Vasculature, Redness of the Skin, Swelling.

Clinical outcomes of posterior scleral reinforcement in Chinese high myopia children

We aim to observe the posterior scleral reinforcement (PSR) clinical outcomes of children with high myopia and analyze the retinal vessel alteration before and after PSR by using angiography optical coherence tomography (angio-OCT). Fifty-six pediatric participants (112 eyes) clinically diagnosed high myopia were recruited and were treated by PSR in Shanghai Children’s Hospital from June 1, 2021 to May 1, 2023. The average age ranged from 5.42 to 14.83 years (mean 8.83 years) and mean follow up duration was 8.7 months (3–24 months). The axial length (AL) was significantly shortened after PSR (p < 0.05). The spherical equivalent (SE) and the best-corrected visual acuity (BCVA) were also improved without severe rejection in the follow-up. Compared with baseline, angio-OCT parafoveal vessel indices including vascular area density (VAD) and vascular skeleton density (VSD) on the superficial capillary plexus layer (SCPL), as well as VAD and vessel perimeter index (VPI) on the deep capillary plexus layer (DCPL), were significantly increased after PSR surgery (p < 0.05). VPI on the SCPL, vascular diameter index (VDI) and VSD on the DCPL were also improved without statistical difference after PSR. The VSD on SCPL, VAD on DCPL of the right eyes and the VPI on SCPL of the left eyes were significantly increased after PSR (p < 0.05). PSR surgery can shorten the AL and can stable BCVA and SE in high myopia children. The angio-OCT parameters indicated that the retinal microcirculation supply was significantly improved after PSR.

Microvascular Changes during Viral Infections: A Systematic Review of Studies Using Retinal Vessel Diameter Assessments.

Viral infection frequently affects the cardiovascular system, and vascular disturbances in patients can lead to health complications. One essential component of the cardiovascular system that is vulnerable to the inflammatory effects of viral infections is the microcirculatory system. As a suitable and practical non-invasive method to assess the structure and function of the retinal microcirculation, a proxy for the microcirculatory system, retinal fundus imaging can be used. We examined the impact of viral infections on retinal vessel diameters and performed a systematic analysis of the literature. Our search was carried out on PubMed using predefined search queries. After a methodological filtering process, we were able to reduce the corpus of 363 publications to 16 studies that met the search parameters. We used a narrative review style to summarise the observations. Six studies covered COVID-19, seven described HIV, and three were included in the subgroup called others, covering viruses, such as Dengue Fever and Crimean-Congo Haemorrhagic Fever. Analysis of the literature showed that viral infections are associated with alterations in the retinal vessels' vasoactivity. COVID-19 and other infections cause inflammation-associated the vasodilatation of microvasculature as a short-term effect of the infection. Long COVID-19 as well as HIV are the cause of chronic inflammation impacting microvascular morphology via retinal vessel diameter narrowing. The review emphasises the importance of the understudied area of viral infections' effects on retinal microcirculation. Continuous research in this area is needed to further verify retinal fundus imaging as an innovative tool for the optimal diagnosis of microvascular changes. As changes in the microvasculature precede changes in bigger arteries, the early detection of microvascular changes can go a long way in reducing the morbidity and mortality associated with cardiovascular diseases.

Retinal small vessel pathology is associated with disease burden in multiple sclerosis

Background: Alterations of the superficial retinal vasculature are commonly observed in multiple sclerosis (MS) and can be visualized through optical coherence tomography angiography (OCTA). Objectives: This study aimed to examine changes in the retinal vasculature during MS and to integrate findings into current concepts of the underlying pathology. Methods: In this cross-sectional study, including 259 relapsing–remitting MS patients and 78 healthy controls, we analyzed OCTAs using deep-learning-based segmentation algorithm tools. Results: We identified a loss of small-sized vessels (diameter < 10 µm) in the superficial vascular complex in all MS eyes, irrespective of their optic neuritis (ON) history. This alteration was associated with MS disease burden and appears independent of retinal ganglion cell loss. In contrast, an observed reduction of medium-sized vessels (diameter 10–20 µm) was specific to eyes with a history of ON and was closely linked to ganglion cell atrophy. Conclusion: These findings suggest distinct atrophy patterns in retinal vessels in patients with MS. Further studies are necessary to investigate retinal vessel alterations and their underlying pathology in MS.

Determination of pulmonary vessel alteration in Chinese male smokers by quantitative computed tomography measurements: a retrospective study.

The blood volume of intraparenchymal vessels is reported to be increased in smokers. However, the blood volume can be affected by many confounders besides tobacco exposure. This study aimed to investigate the association between cigarette smoking and pulmonary blood volume after adjusting the related factors in a large cohort of Chinese males. In this retrospective study, male participants admitted to the First Affiliated Hospital of Xi'an Jiaotong University for annual health assessment between February 2017 and February 2018 were enrolled. All subjects underwent non-contrast chest computed tomography (CT) scans, and 152 subjects underwent a review CT scan 2-3 years later. A three-dimensional approach was employed to segment the lung and intrapulmonary vessels and quantitative CT (QCT) measurements, including lung volume (LV), intrapulmonary vessel volume (IPVV), low-attenuation area <-950 Hounsfield unit (LAA-950 and LAA-950%), and mean lung density (MLD). Linear regression was used to estimate the association between IPVV and the smoking index (SI). A paired t-test was used to compare the QCT parameters between the initial and follow-up CT scans. A total of 656 male participants were enrolled and classified into three subgroups: non-smokers (n=311), current smokers (n=267), and former smokers (n=78). The IPVV of current smokers (134.62±23.96 vs. 120.76±25.52 mL) and former smokers (130.79±25.13 vs. 120.76±25.52 mL) were significantly larger than that of non-smokers (P<0.05). A higher SI was associated with greater IPVV [non-standardized coefficient: 0.167, 95% confidence interval (CI): 0.086-0.248]. For current smokers, the IPVV of the follow-up scan significantly increased compared to its baseline scan (135.49±28.60 vs. 129.73±29.75 mL, t=-2.326, P=0.02), but for the non-smokers and former smokers, the IPVV of the follow-up scan did not increase or decrease compared to the baseline scan (P>0.05). Pulmonary vascular volumes detectable on non-contrast CT are associated with cigarette exposure, and smoking cessation may prevent pulmonary vasculature remodeling.

Integrative Bioinformatics-Gene Network Approach Reveals Linkage between Estrogenic Endocrine Disruptors and Vascular Remodeling in Peripheral Arterial Disease.

Vascular diseases, including peripheral arterial disease (PAD), pulmonary arterial hypertension, and atherosclerosis, significantly impact global health due to their intricate relationship with vascular remodeling. This process, characterized by structural alterations in resistance vessels, is a hallmark of heightened vascular resistance seen in these disorders. The influence of environmental estrogenic endocrine disruptors (EEDs) on the vasculature suggests a potential exacerbation of these alterations. Our study employs an integrative approach, combining data mining with bioinformatics, to unravel the interactions between EEDs and vascular remodeling genes in the context of PAD. We explore the molecular dynamics by which EED exposure may alter vascular function in PAD patients. The investigation highlights the profound effect of EEDs on pivotal genes such as ID3, LY6E, FOS, PTP4A1, NAMPT, GADD45A, PDGF-BB, and NFKB, all of which play significant roles in PAD pathophysiology. The insights gained from our study enhance the understanding of genomic alterations induced by EEDs in vascular remodeling processes. Such knowledge is invaluable for developing strategies to prevent and manage vascular diseases, potentially mitigating the impact of harmful environmental pollutants like EEDs on conditions such as PAD.

Recent progress in alleviating orthodontic discomfort: Mechanism and management-the state of evidence

Orthodontic treatment has demonstrated efficacy in enhancing dental health and rectifying tooth misalignments. Nevertheless, patients experience substantial discomfort and distress. Advancements in orthodontic technology and treatment procedures have led to a decrease in orthodontic discomfort. Orthodontic discomfort refers to the inflammation that occurs due to the obstruction of blood vessels by orthodontic force. This leads to inflammatory responses, which encompass alterations in blood vessels, recruitment of inflammatory and immune cells, and heightened sensitivity of nerves along with the release of chemicals that promote inflammation. The body's inherent analgesic systems ultimately regulate the inflammatory response, thereby diminishing pain. Orthodontic pain signals are transmitted by three-order neurons, beginning with the trigeminal neuron located in the trigeminal ganglia. The signals subsequently arrive at the trigeminal nucleus caudalis located in the medulla oblongata, as well as the ventroposterior nucleus in the thalamus, where the sensation of pain is perceived. The processing of orthodontic pain involves the interplay of emotion, cognition, and memory in many parts of the brain. The structures encompassed in this list are the insular cortex, amygdala, hippocampus, locus coeruleus, and hypothalamus. The inherent analgesic neuronal pathway of the periaqueductal gray and dorsal raphe regions alleviates orthodontic discomfort. Various techniques are employed to manage orthodontic discomfort. These therapies encompass pharmacological, mechanical, behavioral, and low-level laser treatments. Nonsteroidal anti-inflammatory medicines (NSAIDs) alleviate pain, but their impact on tooth movement remains uncertain. Additional research is required to establish the effectiveness of alternative modalities. Gene therapy provides a new, practical, and hopeful approach to treating orthodontic pain. This article explores new advancements and techniques that have enhanced the level of comfort experienced by orthodontic patients.

Reduced Retinal Blood Vessel Densities Measured by Optical Coherence Tomography Angiography in Keratoconus Patients Are Negatively Correlated with Keratoconus Severity.

Keratoconus (KC) is the most common corneal ectasia. Optical coherence tomography angiography (OCT-A) is a relatively new non-invasive imaging technique that allows the visualization and quantification of retinal and choriocapillary blood vessels. The aim of this study is to assess retinal and choriocapillary vessel density (VD) differences between KC patients and healthy controls and to investigate correlations between VD and KC severity. Fifty-two eyes were included in this exploratory study: twenty-six eyes from 26 KC patients and twenty-six eyes from 26 age- and gender-matched healthy controls. All patients underwent Scheimpflug corneal topography with Pentacam, axis lengths measurement and optical coherence tomography angiography (OCT-A). The thinnest spot in corneal pachymetry, maximum K (Kmax) and KC severity indices from the Belin/Ambrósio enhanced ectasia display (BAD) were also assessed. There was a distinct reduction particularly in the retinal VD of the superficial capillary plexus (SCP). Correlation analyses showed strong and moderate negative correlations between the VD in the macular SCP and BAD KC scores and between the SCP VD and Kmax. There was no difference in retinal thickness between the KC and healthy controls. With this study, further evidence for altered VD measurements by OCT-A in KC patients is given. For the first time, we demonstrated negative correlations between BAD KC scores and retinal blood vessel alterations. A major limitation of the study is the relatively small sample size. Since an artefactual reduction of the quantitative OCT-A measurements due to irregular corneal topography in KC must be assumed, it remains to be investigated whether there are also actual changes in the retinal microcirculation in KC.

CbPPGGAN: A Generic Enhancement Framework for Unpaired Pulse Waveforms in Camera-Based Photoplethysmography.

Camera-based photoplethysmography (cbP PG) is a non-contact technique that measures cardiac-related blood volume alterations in skin surface vessels through the analysis of facial videos. While traditional approaches can estimate heart rate (HR) under different illuminations, their accuracy can be affected by motion artifacts, leading to poor waveform fidelity and hindering further analysis of heart rate variability (HRV); deep learning-based approaches reconstruct high-quality pulse waveform, yet their performance significantly degrades under illumination variations. In this work, we aim to leverage the strength of these two methods and propose a framework that possesses favorable generalization capabilities while maintaining waveform fidelity. For this purpose, we propose the cbPPGGAN, an enhancement framework for cbPPG that enables the flexible incorporation of both unpaired and paired data sources in the training process. Based on the waveforms extracted by traditional approaches, the cbPPGGAN reconstructs high-quality waveforms that enable accurate HR estimation and HRV analysis. In addition, to address the lack of paired training data problems in real-world applications, we propose a cycle consistency loss that guarantees the time-frequency consistency before/after mapping. The method enhances the waveform quality of traditional POS approaches in different illumination tests (BH-rPPG) and cross-datasets (UBFC-rPPG) with mean absolute error (MAE) values of 1.34 bpm and 1.65 bpm, and average beat-to-beat (AVBB) values of 27.46 ms and 45.28 ms, respectively. Experimental results demonstrate that the cbPPGGAN enhances cbPPG signal quality and outperforms the state-of-the-art approaches in HR estimation and HRV analysis. The proposed framework opens a new pathway toward accurate HR estimation in an unconstrained environment.

The glymphatic system and cerebral small vessel disease

ObjectivesCerebral small vessel disease is a group of pathologies in which alterations of the brain's blood vessels contribute to stroke and neurocognitive changes. Recently, a neurotoxic waste clearance system composed of perivascular spaces abutting the brain's blood vessels, termed the glymphatic system, has been identified as a key player in brain homeostasis. Given that small vessel disease and the glymphatic system share anatomical structures, this review aims to reexamine small vessel disease in the context of the glymphatic system and highlight novel aspects of small vessel disease physiology. Materials and methodsThis review was conducted with an emphasis on studies that examined aspects of small vessel disease and on works characterizing the glymphatic system. We searched PubMed for relevant articles using the following keywords: glymphatics, cerebral small vessel disease, arterial pulsatility, hypertension, blood-brain barrier, endothelial dysfunction, stroke, diabetes. ResultsCerebral small vessel disease and glymphatic dysfunction are anatomically connected and significant risk factors are shared between the two. These include hypertension, type 2 diabetes, advanced age, poor sleep, obesity, and neuroinflammation. There is clear evidence that CSVD hinders the effective functioning of glymphatic system. ConclusionThese shared risk factors, as well as the model of cerebral amyloid angiopathy pathogenesis, hint at the possibility that glymphatic dysfunction could independently contribute to the pathogenesis of cerebral small vessel disease. However, the current evidence supports a model of cascading dysfunction, wherein concurrent small vessel and glymphatic injury hinder glymphatic-mediated recovery and promote the progression of subclinical to clinical disease.

Quantitative Assessment Characteristics of Small Pulmonary Vessel Remodelling in Populations at High Risk for COPD and Smokers Using Low-Dose CT.

To explore the morphological alterations in small pulmonary vessels in populations at high risk for chronic obstructive pulmonary disease (COPD) and smokers based on multiple computed tomography (CT) quantitative parameters. A total of 1969 Three Major Chest Diseases Screening Study participants with available demographic data and smoking history who underwent low-dose chest CT from 2018 to 2020 were included. All subjects were divided into normal, high risk for COPD, and COPD groups according to their pulmonary function test (PFT) results. Furthermore, the three groups were further subdivided into never-smokers, current smokers, and former smokers subgroups according to their smoking history. Quantitative parameters, such as the number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels, were extracted by computer software. Differences in small pulmonary vessel parameters among the groups were compared using two-way ANOVA. The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the group at high risk for COPD were lower than those in the normal group (P<0.05). The number, area at 6 mm~24 mm subpleura and volume of small pulmonary vessels in the COPD group were higher than those in the normal group (P<0.05). The number, area of small pulmonary vessels at 6 mm~12 mm subpleura in current smokers with high risk for COPD were higher than those in former smokers with high risk for COPD (P<0.05). The number, area, and volume of small pulmonary vessels in populations at high risk for COPD were decreased. Smoking cessation may impede structural changes in small pulmonary vessels in populations at high risk for COPD.

Role of heparin‐binding mediators in the resistance to anti‐VEGF therapies in diabetic retinopathy

Aims/Purpose: Anti‐vascular endothelial growth factor (VEGF) drugs represent the standard of care for diabetic retinopathy (DR); however, lack of response occurs in approximately 50% of patients. Aim of our work is the identification of the mediators responsible for anti‐VEGF drug resistance.Methods: Vitreous samples were collected from anti‐VEGF non‐responder (non‐RES) patients; non‐RES heat‐inactivated (HI) vitreous were used as control. To develop a new orthotopic model of DR, non‐RES or HI vitreous were injected intravitreally in mice and after 48 h retinas were explanted and analysed. The composition of non‐RES vitreous was assessed by an angio‐inflammatory protein array. The effect of the inhibition of the bioactive heparin‐binding mediators (HBMs) present in non‐RES vitreous was evaluated in the endothelial spheroid sprouting assay.Results: Mouse orthotopic intravitreal injection of non‐RES vitreous upregulated the expression of pro‐angiogenic/pro‐inflammatory mediators; moreover, it induced alterations of retinal vessels, accumulation of inflammatory infiltrate, and activation of astrocyte gliosis. Notably, HI vitreous was ineffective, pointing to a proteinaceous nature of the non‐RES vitreal mediators acting on mouse retinae. In this context, the blockade of vitreal HBMs mediated by the biotechnological heparin‐like molecule K5‐N, OS (H) or by the pentapeptide Boc2, completely abrogated the activity of non‐RES samples. It is worth noticing that the potency of anti‐HBP compounds was significantly higher than the anti‐VEGF ranibizumab, which was partially effective only at the clinically relevant and saturating concentration of 10 μM, with no further improvement at a double dose.Conclusions: Our data show that VEGF is only part of a complex machinery regulating angiogenesis, inflammation and oedema formation during DR and that drug resistance is due to the activation of compensatory mechanisms mediated by HBMs besides VEGF.

Retinal and Conjunctival Vessels in the Diagnosis and Assessment of Behcet's Disease: A New Approach.

The study aimed to investigate the alterations of retinal and conjunctival vessels in patients with Behcet's disease (BD). In this case-control study, 17 patients (34 eyes) diagnosed with BD and 17 healthy volunteers (34 eyes) matched by age, sex, blood pressure, and intraocular pressure were recruited. Optical coherence tomography angiography examinations were performed to calculate the vessel density of the retina and conjunctiva according to different sizes of vessels and different zones divided by three segmentation methods of the retina: hemispheric segmentation, Early Treatment Diabetic Retinopathy Study, and central annulus segmentation. The vessel densities of the superficial macrovascular (P = 0.050), superficial microvascular (P < 0.001), superficial total microvascular (P < 0.001), deep total microvascular (P < 0.001), and deep total microvascular (P < 0.001) were significantly lower in the BD group. The conjunctival vessel density was significantly higher in the BD group (P < 0.001). The receiver operating characteristic curve analysis showed that the area under the curve of vessel density of the superior right (0.993, 95% CI 0.980-1) and right zones (0.996, 95% CI 0.987-1) were the largest in the superficial and deep retina, respectively. Otherwise, the area under the curve of conjunctival vessel density was 0.728 (95% CI 0.607-0.848). In patients with BD, retinal vessel density decreases, while conjunctival vessel density increases. Optical coherence tomography angiography provides a new noninvasive and quantitative assessment for retinal and conjunctival vessels. [Ophthalmic Surg Lasers Imaging Retina 2024;55:13-21.].

Super-Resolution Ultrasound Imaging of Renal Vascular Alterations in Zucker Diabetic Fatty Rats during the Development of Diabetic Kidney Disease.

Individuals with diabetes at risk of developing diabetic kidney disease (DKD) are challenging to identify using currently available clinical methods. Prognostic accuracy and initiation of treatment could be improved by a quantification of the renal microvascular rarefaction and the increased vascular tortuosity during the development of DKD. Super-resolution ultrasound (SRUS) imaging is an in vivo technique capable of visualizing blood vessels at sizes below 75 µm. This preclinical study aimed to investigate the alterations in renal blood vessels' density and tortuosity in a type 2 diabetes rat model, Zucker diabetic fatty (ZDF) rats, as a prediction of DKD. Lean age-matched Zucker rats were used as controls. A total of 36 rats were studied, subdivided into ages of 12, 22, and 40 weeks. Measured albuminuria indicated the early stage of DKD, and the SRUS was compared with the ex vivo micro-computed tomography (µCT) of the same kidneys. Assessed using the SRUS imaging, a significantly decreased cortical vascular density was detected in the ZDF rats from 22 weeks of age compared to the healthy controls, concomitant with a significantly increased albuminuria. Already by week 12, a trend towards a decreased cortical vascular density was found prior to the increased albuminuria. The quantified vascular density in µCT corresponded with the in vivo SRUS imaging, presenting a consistently lower vascular density in the ZDF rats. Regarding vessel tortuosity, an overall trend towards an increased tortuosity was present in the ZDF rats. SRUS shows promise for becoming an additional tool for monitoring and prognosing DKD. In the future, large-scale animal studies and human trials are needed for confirmation.

Morphological Appearance of Blood Vessels of Organs in Diabetes Mellitus

This article explores the morphological alterations in blood vessels within various organs in individuals with diabetes mellitus. Diabetes mellitus, a chronic metabolic disorder, exerts a profound impact on vascular health, resulting in structural changes that contribute to a range of complications. Through a comprehensive review of existing literature and histological studies, this article delves into the diverse manifestations of vascular morphological changes in organs such as the heart, kidneys, eyes, and peripheral tissues. Understanding these alterations is crucial for elucidating the pathophysiological mechanisms underlying diabetic complications and developing targeted therapeutic strategies to mitigate their effects.

C64 REDUCTION IN EJECTION AND PRE–EJECTION PERIODS ARE PREDICTIVE OF MORTALITY IN AL AND ATTR HEART AMYLOIDOSIS

Abstract Background Amyloidosis is a systemic disease caused by fibrillary misfolded protein deposition in several organs including the heart. Cardiac deposition is the leading cause of death in these patients. Echocardiography is the imaging technique mostly used to study cardiac amyloidosis. Many studies tried to identify earlier markers to stratify the mortality risk. Heart stiffness is the main issue leading the heart dysfunction. However, few data are available on the possible role of connection between heart and possible vessels alterations. Purpose: Aim of this study was to evaluate heart stiffness using Ventricular–arterial coupling (VAC) for relationship between heart and vessel tree. Methods We studied 58 patients (22 F and 36 M, aged 67.14± 12.49) with AL or ATTR amyloidosis and heart involvement. They were 42 AL and 16 ATTR patients. All patients were evaluated before treatment with a complete history, physical exam, serum markers of disease, and echocardiogram. The abdominal fat biopsy to confirm amyloid deposition was performed before treatment. Among all patients, 18 died with a mean OS of 12 months [IQR 1–24 months]. Results At baseline, VAC was increased in died patients (alive 1.53 ± 0.43 vs died 2.06 ± 1.73, p=0.09) but was ineffective to predict the risk of mortality (ROC analysis AUC 0.54, p=0.57). By analysing ejection and pre–ejection periods we found that they were both increased in alive patients (p=0.0016 and p=0.0072, respectively). Moreover, these periods were effective in prediction of the death risk (ejection time AUC 0.81, cut–off 239 msec, sensitivity 61.54% and specificity 88.24%; pre–ejection time AUC 0.75, cut–off 82 msec, sensitivity 84.62% and specificity 58.82%). No difference in VAC, ejection time or pre–ejection time were found comparing AL to ATTR, nor both parameters had a predictive role. Conclusion Amyloidosis induces an increase in heart stiffness and reduces heart contractility. This causes a reduction of peripheral blood flow and a worsening in heart failure. We demonstrated that this mechanism affects the capacity to pump blood in vessels due the reduction in time for loading during the systole. These results may predict the mortality with a significant sensitivity and specificity, regardless of the type of amyloidosis.