Vascular Alterations Research Articles

Early Diabetic Retinopathy Evaluation With OCTA: A Study on Vascular Branching and Fragmentation.

The purpose of this study was to quantitatively evaluate the branching patterns and vascular fragmentation features in preclinical and early diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). OCTA metrics, including branch node number (BNN), branch node density (BND), end point number (EPN), end point density (EPD), fragmented vessel segment count (FVSC), and fragmented vascular length ratio (FVLR), were measured in foveal and parafoveal regions within superficial and deep vascular plexus (SVP and DVP) in the retina. Compared to healthy control (HCs), both BNN and BND exhibited a significant decrease in individuals with mild DR across both retinal layers, and also in diabetes mellitus without DR (no DR) within DVP. EPD showed a significant increase in mild DR cases compared to HCs, except for the foveal region in SVP; however, EPN did not demonstrate a significant difference among the three groups. Increases in both FVSC and FVLR were significant across all areas and in both layers of the retina. Notably, these metrics showed more pronounced differentiation in the DVP than the SVP. Foveal BND and BNN in DVP reveal vascular alterations indicative of preclinical DR. Indicators such as EPD, FVSC, and FVLR in DVP correlate with early DR changes and are useful for its early detection. These initial findings demonstrate the potential and benefits of these quantitative OCTA indices for delineating DR-associated alterations in the retinal microvasculature, indicating their potential clinical utility for improved DR screening.

Investigation of choroidal vascular alterations in eyes with myopia using ultrawidefield optical coherence tomography angiography

Background/aimsThe study aims to evaluate choroidal vascular changes in younger patients with myopia using ultrawidefield swept-source optical coherence tomography angiography (SS-OCTA).MethodsOverall, 724 eyes of 362 participants (177 males, 185 females,...

Retinal vascular alterations are associated with cognitive function and neuroimaging in white matter hyperintensities

AimTo reveal alterations in retinal structure, vessels, and function, and their association with cognitive function and neuroimaging in white matter hyperintensities (WMH). MethodsThis study enlisted WMH and age-matched healthy controls (HC). All participants underwent six different tests: magnetic resonance imaging (MRI) of the brain, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), fundus photography, optical coherence tomography (OCT), and visual field testing. Visual field can reflect the function of optic nerve and retina. The peripapillary retinal nerve fiber layer (p-RNFL) was analyzed using OCT. Image J software was employed to measure retinal vascular caliber in fundus photographs and to compute the central retinal artery equivalent (CRAE), central retinal venous equivalent (CRVE) and arteriole-to-venule ratio (AVR). ResultsA total of 90 WMH patients and 93 HC participants. In comparison with the HC, the WMH group exhibited reduced cognitive function scores (MoCA: P < 0.001; MMSE: P < 0.001), narrower retinal arteries (P < 0.001), smaller AVR (P < 0.001) and thinner p-RNFL thickness (total: P = 0.026; temporal: P = 0.006). About visual field, both univariate and multivariate analysis showed that mean sensitivity decreased, and mean defect increased in WMH group (P < 0.05). Additionally, correlation analysis indicated a positive correlation between CRAE and AVR with MMSE and MoCA score (r = 0.424–0.57, P < 0.001) and a negative correlation with Fazekas score (CRAE: r = −0.515, P < 0.001; AVR: r = −0.554, P < 0.001), and p-RNFL was negatively correlated with Fazekas score (total p-RNFL: r = −0.192, P = 0.009; temporal p-RNFL: r = −0.217, P = 0.003). Notably, no significant correlation was found between cognitive function and p-RNFL. ConclusionWMH group exhibit narrower retinal arteries, smaller arteriole-to-venule ratio, damaged p-RNFL and visual function. These alterations in retinal vessels are associate with both neuroimaging and cognitive function. Our results suggest that retinal imaging could serve as a valuable instrument for evaluating WMH and provides some new approaches to study the characteristic markers of WMH.

Choroidal and retinal alteration after long-term use of tadalafil: a prospective non-randomized clinical trial.

The purpose of this study is to investigate choroidal and retinal vascular features in patients taking PDE5is by measuring dynamic vascular alterations and neurostructural features of the retina before and after oral tadalafil administration. The current clinical research involved 22 patients treated with tadalafil 20 mg on alternate days (OAD) after nerve-sparing robotic radical prostatectomy (NS-RARP) for prostate cancer. Patients underwent SD-OCT to assess ganglion cell complex (GCC), retinal nerve fiber layer (RNFL), and subfoveal choroidal thickness (SFCT), as well as OCTA to assess superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC), foveal avascular zone (FAZ), and radial peripapillary capillary thickness (RPC). All patients were evaluated at baseline (t0), and 3 (t1) and 6 (t2) months after the use of oral tadalafil. A statistically significant reduction in DCP and CC vessel density was found at t2 compared to baseline. According to the SFCT parameter, a statistically significant increase was observed from t0 to t1, and from t1 to t2. GCC parameter increased at t2 compared to baseline in a statistically significant way. No statistically significant differences were recorded between t0, t1 and t2 for the SCP, RPC, FAZ area, RNFL parameter. Retinal and optic disc toxicity may be detected using modifications of capillary vessel density. Further studies are needed to detect the possible progression or regression of ocular or systemic vascular complications in long-term follow-up.

Abstract 4136025: Establishing normal values for central systolic blood pressure and augmentation index in healthy young people

Background: The process of cardiovascular disease (CVD), a leading cause of death worldwide, commences in childhood. Increasing evidence indicates that early exposure to CVD risk factors in childhood is associated with impaired arterial distensibility and other vascular alterations, suggesting that vascular ageing biomarkers, that capture the deterioration in vascular structure and function, can be used to identify children at risk. However, the identification of early vascular alterations in the young is hampered by the lack of a recognized, vascular biomarker that can be used in clinical practice. The Youth Vascular Consortium, an international collaborative open resource has been established to answer these gaps by analysing different biomarkers, including central systolic blood pressure (cSBP) and augmentation index (AIx). These two non-invasive measures are related to CVD and end-organ damage, however, their assessment in clinical practice is limited by the lack of established normal values. Aims: We aimed to establish cSBP and AIx normal values in a young, healthy, international population. Methods: The Consortium collected data on 36,973 participants from 24 countries. We included 14,476 and 5,047 subjects respectively for the cSBP and AIx populations. Subjects were free of any CVD or cardiovascular risk factors. Data were collected from participants aged from 1 to 40 years. Normal values of cSBP and AIx were calculated as percentiles stratified by age and sex. Percentiles curves were generated using generalised additive models. Results: The cSBP percentile curves increase with the same trend for both males and females until age 13 years. Over this age, males experience greater cSBP than females. This is in contrast to AIx, which decreases with the same trend in both sexes until 15 years of age, after which females experience increased AIx. Conclusion: Normal values of cSBP and AIx in healthy young are now available according to age and sex with a wide geographical representation. Incorporating these values into clinical practice for young could facilitate their utilization as targets for the introduction and monitoring of interventions.

Abstract 4136884: Incidence and Characteristics of Peri-Procedural Complications of Cardiac Implantable Electrical Devices in Breast Cancer Survivors

Introduction: Breast cancer (BC) is the most common non-cutaneous cancer in women. Several BC treatments increase the risk of conduction abnormalities and heart failure, potentially requiring cardiac implantable electrical devices (CIEDs). Due to vascular access devices, surgical management, and chest wall radiation, these patients are subject to upper extremity vascular alterations. There is limited data regarding CIED use in this population. Research question: Do patients with BC and CIEDs have different procedural approaches or complications compared to the general population? Aims: This study aimed to evaluate CIED placement and periprocedural complications in patients with a history of BC. Methods: This was a retrospective study of CIEDs placed at our institution between 2005 and 2023. Patients with a diagnosis of BC prior to time of placement were included. Complications included those within 30 days of the procedure. Results: We analyzed 109 female patients (median age of 73 years, IQR 66-80) who received pacemaker (PPM, 58.7%), cardiac resynchronization therapy defibrillator (CRT-D, 22%), implantable cardioverter defibrillator (ICD, 16.5%), or cardiac resynchronization therapy pacemaker (CRT-P, 2.8%). The median time from cancer diagnosis to device placement was 13 years (IQR 7-21). Oncologic therapies are included in Figure 1. In patients with unilateral cancer, most devices (78.4%) were placed contralaterally, with 32% of all devices being right sided. Anatomy related to chemotherapy port altered intraoperative approach in 2 cases and bilateral lymph node dissection necessitated subcutaneous ICD in 1 case. Complications were noted in 12 patients (11%) and included hematoma, lead revision, upper extremity DVT, pericardial effusion, stress cardiomyopathy, perforation, site infection, and worsening of chronic lymphedema. Conclusions: BC survivors undergoing CIED placement appear to be at higher risk of periprocedural complications when compared to the general population. They are more likely to undergo right sided device placement to avoid vascular access ipsilateral to prior surgery or radiation. Further studies are required to understand the long-term outcomes of CIED placement in this cohort of patients.

TMIC-47. HUMAN BLOOD-BRAIN TUMOR BARRIER ON A CHIP TO INVESTIGATE PERSONALIZED TREATMENT FOR GLIOBLASTOMA PATIENTS

Abstract The inherent characteristics of glioblastoma multiforme (GBM), including tumoral heterogeneity and invasive capacity, combined with the presence of the blood-brain tumor barrier (BBTB), present challenges in developing effective treatment for GBM. Especially, the margins of GBM, where GBM cells infiltrate normal brain tissue, exhibit high resistance to therapies. Despite the difficulties in controlling tumor progression from this region, the GBM margin remains a critical area to be studied. Here we report a microengineered model that mimics the BBTB within the GBM margin, incorporating a 3D network of normal astrocytes and GBM cells isolated from patients newly diagnosed with GBM. The interaction between GBM cells and stromal cells results in increased vascular permeability, reactive gliosis, and alterations in astrocyte behavior to foster tumor invasiveness and progression. We compare patient-specific tumor responses to conventional chemotherapy in our BBTB on a chip model with clinical outcomes, demonstrating the capability of the model to predict personalized drug responses. Our BBTB model may serve as a personalized tool to examine the interactions between tumors and normal brain tissue, ultimately facilitating the screening of personalized medicine for GBM treatment.

NIMG-26. GLIOBLASTOMA TISSUE INVASION MAPPING WITH NOVEL HYPOXIA-TARGETED BLOOD OXYGENATION-LEVEL DEPENDENT MRI

Abstract BACKGROUND Glioblastoma is a devastating incurable malignant primary brain tumor exhibiting an erratic growth pattern and brain tissue invasion exceeding the typically depicted contrast-enhancing lesion on MRI. This behaviour is strongly associated with the presence of aberrant vasculature. Advanced clinical neuroimaging techniques, however, have not provided convincing imaging markers to determine glioblastoma tissue infiltration and monitor treatment effects. We investigated a new imaging technique based on blood oxygenation-level dependent (BOLD) MRI contrast with precise hypoxic respiratory targeting in order to better determine tumor tissue invasion not restricted to the typically depicted focal glioblastoma lesion on contrast-enhanced MRI. METHODS A computer-controlled gas blender was used to induce transient and standardized hypoxic stimulus in isocapnic conditions during echo-planar-imaging acquisition in patients with brain tumors.8,9 Data were preprocessed using SPM and in-house written MATLAB scripts. The induced BOLD signal changes were used to calculate %BOLD signal change during hypoxic stimulus with respect to the baseline, contrast to noise (CNR) ratio and goodness-of-fit (Rsquared) for each voxel in the whole-brain and automatically segmented region of interest (contrast-enhancement, necrosis, edema) and overlayed using color-maps onto anatomical high resolution T1. RESULTS Hypoxic targeting during gas modulation could be performed with high reproducibility, caused no discomfort in patients with brain tumors and was able to induce strong signal change during hypoxic stimulus with high contrast-noise ratio and Rsquared. In particular, when compared with other tumors, BOLD hypoxia glioblastoma tissue invasion maps show very distinct hypoxic signal responses in some cases extending beyond the focal -contrast-enhancing- glioblastoma lesion. CONCLUSION The ability to map at voxel level BOLD hypoxia signal patterns may determine a novel therapeutic imaging marker based on structural vascular alterations in the tumour tissue infiltration zone before these become appreciable with standard neuroimaging. This may support a refinement and tailoring of tumor resection and improve follow-up after resection and during treatment i.e. chemoradiotherapy.

Grape seed oil attenuates sodium arsenite-induced gastric, hepatic and colonic damage in Wistar rats

ABSTRACT Arsenic exposure is associated with numerous morbidities due to dysfunction of various organ systems including the gastrointestinal tract. We investigated the protective effect of grape seed oil (GSO) against sodium arsenite (NaAsO2)-induced gastric, hepatic and colonic injuries in rats. Twenty-four male Wistar rats were divided into four groups of six as follows: Group A (control) received saline; group B received NaAsO2 (2.5 mg/kg) orally for 7 days; group C were treated concurrently with NaAsO2 and GSO (2 ml/kg), while group D received only GSO. Administration of NaAsO2 induced significant (p < 0.05) increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST); increased periodic acid Schiff (PAS) staining for mucus and increased goblet cell numbers in the stomach and colon; inflammatory cell infiltration and vascular congestion and alterations in the fecal bacterial flora. GSO supplementation generally promoted a reversal of changes induced by NaAsO2 towards control levels. Additionally, there was increased immunohistochemically detected expression of colonic B-cell lymphoma-1 (Bcl-2) and cytokeratins AE1/AE3, but reduced expression of mucin 1 (MUC1) and carcinoembryonic antigen (CEA) in NaAsO2 + GSO and GSO treated rats when compared with the NaAsO2 group. These results suggest that GSO promoted anti-inflammatory processes in the liver, stomach and colon, as well as opposing apoptosis in the colon, resulting in significant attenuation of damage to these tissues.

Artificial intelligence-based prediction of neurocardiovascular risk score from retinal swept-source optical coherence tomography–angiography

The recent rise of artificial intelligence represents a revolutionary way of improving current medical practices, including cardiovascular (CV) assessment scores. Retinal vascular alterations may reflect systemic processes such as the presence of CV risk factors. The value of swept-source retinal optical coherence tomography–angiography (SS OCT-A) imaging is significantly enhanced by image analysis tools that provide rapid and accurate quantification of vascular features. We report on the interest of using machine-learning (ML) and deep-learning (DL) models for CV assessment from SS OCT-A microvasculature imaging. We assessed the accuracy of ML and DL algorithms in predicting the CHA2DS2-VASc neurocardiovascular score based on SS OCT-A retinal images of patients from the open-source RASTA dataset. The ML and DL models were trained on data from 491 patients. The ML models tested here achieved good performance with area under the curve (AUC) values ranging from 0.71 to 0.96. According to a classification into two neurocardiovascular risk groups, the EfficientNetV2-B3, a well suited DL model for retinal OCT-A images, predicted risk correctly in 68% of cases, with a mean absolute error (MAE) of approximately 0.697. Our models enable a confident prediction of the CHA2DS2-VASc score from SS OCT-A imaging, which could be a useful tool contributing to the assessment of neurocardiovascular profiles in the future.

Exploring quercetin's protective potential against the pro-inflammatory effects of silver nanoparticles in C57BL/6J mice

The increasing prevalence of silver nanoparticles (AgNP) in various applications has sparked concerns about their potential adverse effects on human health. Hence, it is crucial to devise strategies to minimize their detrimental effects. Quercetin, a naturally occurring flavonoid present in human diet is known for its broad biological effects, including anti-inflammatory properties. Considering this, quercetin could serve as a promising strategy to protect the body against the harmful effects of AgNP. Thus, this study aimed to evaluate the potential protective role of quercetin against the deleterious effects induced by 5 nm polyvinylpyrrolidone (PVP)–AgNP in C57BL/6J mice. Using a novel administration technology (HaPILLness), mice were given a daily oral dose of AgNP at 1 mg/kg body weight (bw) or 10 mg/kg bw for 14 days, combined with daily IP injections of quercetin at 1 mg/kg bw. Our findings demonstrate that quercetin effectively attenuated the AgNP-induced intestinal inflammatory response, as demonstrated by reduced histological vascular and cellular alterations, along with a notable decrease in cytokine production, attributed to the inhibition of the nuclear factor (NF)-кB inflammatory pathway. Quercetin's protective effects extended to the liver and lungs, by reversing changes in the inflammatory and antioxidant markers cluster of differentiation (CD)4, superoxide dismutase 1 (SOD1) and catalase.

Chlorogenic Acid Alleviates Inflammation and Fibrosis in a Murine Model of Bleomycin-Induced Systemic Sclerosis: A Histological Analysis

Background/Objectives: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by cutaneous and visceral fibrosis, vascular alterations, and a persistent inflammatory response. Despite advances in understanding the pathogenic mechanisms underlying SSc, current therapeutic options remain limited. Chlorogenic acid (CGA) is a polyphenol widely distributed in plants and has shown antioxidant, anti-inflammatory, and antifibrotic properties. However, its therapeutic potential in SSc has not been investigated yet. Methods: A model of SSc was established by administering bleomycin (BLM) at 100 U/kg to CD1 mice via an osmotic minipump. After fourteen days of BLM administration, CGA (60 mg/kg) was intragastric administered on consecutive days until day 20. On day 21, all mice were sacrificed. The effect of CGA was histologically evaluated by hematoxylin and eosin and Masson’s trichrome staining. Results: CGA treatment significantly attenuated dermal fibrosis in the BLM-induced mice model of SSc by reducing histopathological damage, including increased dermal thickness, inflammation, collagen deposition, and SSc-associated pulmonary fibrosis. Conclusions: The evidence shows that CGA attenuates BLM-induced SSc in a mice model and strongly suggests that CGA may be a promising compound for the treatment of SSc.

Evaluating the impact of polycythemia vera on retinal and optic nerve head microvascularity: An OCTA study.

This study aims to assess the impact of polycythemia vera (PV) on retinal and optic nerve head (ONH) vessel density (VD) parameters, macular ganglion cell complex (mGCC) thickness, and retinal nerve fiber layer (RNFL) thickness compared to healthy controls. Forty eyes of 20 patients with PV and 40 eyes of 20 age-gender-matched healthy controls underwent comprehensive ophthalmologic assessments and optic coherence tomography angiography (OCTA). RNFL and macular GCC measurements were obtained simultaneously with vascular parameters by AngioVue OCTA using the single-scan protocol. Peripapillary VD was examined across eight sectors, whereas parameters including RNFL, GCC, and macular VD were analyzed in four quadrants. Patients with PV exhibited significant reductions in the average RNFL thickness ( P = 0.014) and RNFL thickness in superior ( P < 0.001) and inferior ( P = 0.003) quadrants compared to controls. Additionally, mGCC thickness in all quadrants significantly reduced in the PV group ( P < 0.001). ONH VD parameters, including whole-image VD ( P < 0.001) and peripapillary VD ( P < 0.001), were significantly reduced in patients with PV. Similarly, macular VD parameters were significantly lower in the PV group ( P < 0.001). This study highlights substantial vascular and structural alterations in the retina and ONH of patients with PV compared to healthy controls. These changes likely stem from microvascular dysfunction associated with PV. These findings suggest further research to understand the underlying mechanisms and develop targeted therapeutic strategies for managing ocular complications in patients with PV.

A new phenotype or retinal involvement in Steinert Disease: a case report.

To report a case illustrating the association of Steinert Disease (SD) with peripheral retinal non-perfusion areas and epiretinal membrane. Case report. A 47-year-old Caucasian female diagnosed with SD was referred for blurred vision in her right eye (RE). She presented bilateral ptosis with deficit of elevator muscle.Dilated fundus examination revealed altered macular reflex, peripheral vascular alterations, and ghost vessels bilaterally. Structural spectral domain optical coherence tomography (SD-OCT) showed an epiretinal membrane with a partial alteration of the foveal profile in the RE. Optical coherence tomography angiography (OCTA) images revealed no evidence of neovascular membrane in the macular region. Fluoresceine angiography (FA) showed retinal peripheral non perfusion areas and leakage in the late phases of the examination. Any retinal alteration should be considered during the ophthalmological examination of patients suffering from type 1 myotonic dystrophy. OCT and fluoresceine angiography should be performed evaluating the SD patient that complains about visual impairment.

Endothelial cell-specific progerin expression does not cause cardiovascular alterations and premature death.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by a mutation in the LMNA gene that provokes the synthesis of progerin, a mutant version of the nuclear protein lamin A that accelerates aging and precipitates death. The most clinically relevant feature of HGPS is the development of cardiac anomalies and severe vascular alterations, including massive loss of vascular smooth muscle cells, increased fibrosis, and generalized atherosclerosis. However, it is unclear if progerin expression in endothelial cells (ECs) causes the cardiovascular manifestations of HGPS. To tackle this question, we generated atherosclerosis-free mice (LmnaLCS/LCSCdh5-CreERT2) and atheroprone mice (Apoe-/-LmnaLCS/LCSCdh5-CreERT2) with EC-specific progerin expression. Like progerin-free controls, LmnaLCS/LCSCdh5-CreERT2 mice did not develop heart fibrosis or cardiac electrical and functional alterations, and had normal vascular structure, body weight, and lifespan. Similarly, atheroprone Apoe-/-LmnaLCS/LCSCdh5-CreERT2 mice showed no alteration in body weight or lifespan versus Apoe-/-LmnaLCS/LCS controls and did not develop vascular alterations or aggravated atherosclerosis. Our results indicate that progerin expression in ECs is not sufficient to cause the cardiovascular phenotype and premature death associated with progeria.

Gradual hypertensive response in aortic alterations and myocardial inflammatory activation in progressing HFpEF in mice

Abstract Introduction Hypertension is the most common comorbidity in patients affected by heart failure with preserved ejection fraction (HFpEF). Early effects of pressure overload and its contribution to the gradual development of cardiac and vascular pathology leading to HFpEF are not well recognized, as patients are diagnosed when the disease has already advanced and show symptoms. Several hypertensive HFpEF mouse models possessing the hallmarks of the clinical-like phenotype are available. Nonetheless, initial and gradual pathological manifestations of hypertensive HFpEF have not been comprehensively described. Purpose This study aimed to investigate the gradual progression of HFpEF phenotype development in mice from the early manifestation of cardiac and vascular pathology to global cardiac dysfunction to multiorgan syndrome in response to hypertension. Methods Hypertensive HFpEF was induced by angiotensin II infusion in C57BL/6JOlaHsd 18-20-week-old male mice that were given low, moderate and high doses (0.5mg/kg/day - 1.5 mg/kg/day) subcutaneously for 4 weeks. Cardiac physiology and alterations in haemodynamics were assessed with echocardiography of heart and aorta, weekly ECG monitoring, and blood pressure measurements from the mouse tail. Extensive histology and immunohistochemistry analyses of cardiac tissue, microvasculature, lungs and kidneys were performed. Results In the low dose group, loss of aortic wall flexibility and presence of aortic root dilatation were detected. This group also demonstrated initiation of concentric remodelling process with the upsurge in macrophage infiltration in myocardium, but the signs of diastolic dysfunction were not yet present. The high dose group exhibited characteristic HFpEF features with diastolic dysfunction, left ventricular hypertrophy and fibrosis. Pathology in cardiac conduction system was noticed in all groups, with prominent ECG waveform abnormalities already on week one. However, only the high dose group experienced non-recovery in impulse propagation, accompanied by significant prolongation of ventricular depolarization. Conclusion This study demonstrates that change in aortic root dimensions and aortic wall dynamics are the first hypertension-sensitive alterations together with myocardial inflammatory cell infiltration that may contribute to myocardial remodelling and subsequent development of HFpEF and systemic effects. Hypertensive angiotensin II-induced HFpEF is a relevant mouse model, recapitulating not only hallmarks of cardiac pathology but also an extensive range of vascular and multiorgan alterations, demonstrating similarities with the clinical phenotype.

Impact of neonatal hyperoxia on the development of the coronary vascular bed: an experimental model for the study of cardiomyopathy associated with premature birth

Abstract Introduction Very preterm birth (PT; &amp;lt;32 weeks of gestation), nearly 2% of all births, leads to short-term complications such as bronchopulmonary dysplasia and retinopathy of prematurity that are driven by compromised organ vascular development. Adults born preterm display an increased risk of ischaemic cardiomyopathy and heart failure. Our group has shown that neonatal rats exposed to hyperoxia, simulating the PT neonatal conditions, develop cardiomyocytes hypertrophy, fibrosis and cardiac dysfunction, or Oxygen-Induced Cardiomyopathy (OIC). Whether cardiac changes also associate with alterations in vascular development in the left ventricle (LV) remains unknown. Purpose We hypothesized that neonatal exposure to hyperoxia impact the development of the LV vascular network. Methods Male pups were exposed to 80% O2 (OIC) or room air (CTRL) from day 3 (P3) to P10 of life. Hearts were collected at P10, 4- and 16 weeks. Arteriolar length and capillary density per cardiomyocyte were measured using stereology (elastin) and immunofluorescence (WGA, α-SMA, CD31). High-resolution 3D reconstruction of the vascular network was achieved by combining fluorescent labelling of coronaries (anti-α-SMA) and capillaries (anti-CD31) with a tissue-cleaning protocol (iDisco+), allowing detailed morphometric characterization of the vascular network. The expression of vascular endothelial growth factors and receptors (VEGFA, VEGFB, VEGFR 1 and 2, NRP1, and PIGF) were quantified by RT-qPCR and Western blots. Differences between groups were analyzed with Student's t-test (P &amp;lt; 0.05) (N = 6 per group). Results At P10, we observed a notable rise in the number of capillaries per cardiomyocyte (0.88 ± 0.05 vs. 0.62 ± 0.02 mm2) and a significant increase in VEGFA (+76%) and NRP1 (+38%) expression in the LV from OIC vs. CTRL rats. By 4 weeks, the OIC group showed a significant reduction in arteriolar length vs. CTRL (6.51 ± 0.76 vs. 9.77 ± 1.12 m/cm3), coupled with an increase in the number of capillaries per cardiomyocyte (1.11 ± 0.05 vs. 0.85 ± 0.03 mm2). VEGFA was decreased (-14%) and PLGF increased (+24%) in the LV of OIC rats. At 16 weeks, the OIC condition displayed a significant increase in the number of capillaries per cardiomyocyte (1.37 ± 0.03 vs. 0.98 ± 0.07 mm2) and a decrease in VEGFA (-23%), along with reduction in its receptors VEGFR1 (-27%), VEGFR2 (-20%) and NRP1 (-17%). Conclusion OIC resulting from neonatal hyperoxia exposure associates with vascular changes in the LV that persist to adulthood. These changes are characterized by a reduction in arteriolar length and an increase in the number of capillaries, accompanied by modulation of the expression of pro-angiogenic VEGFA and receptors. The impact of these vascular alterations on the susceptibility of the LV to ischemic or hypertension-related damage is to be explored. These findings suggest a crucial mechanistic pathway for understanding the risk of cardiac pathologies associated with preterm birth.

Foot Sole Temperature Correlates with Ankle-Brachial Index, Pulse Wave Velocity, and Arterial Age in Diabetic Patients Without Diagnosis of Peripheral Arterial Disease.

Background/Objectives: Some vascular alterations such as peripheral arterial disease (PAD) or arterial stiffness can alter perfusion of the limbs, so we wondered if this is reflected in the temperature of the soles of the feet of diabetic patients who did not have a diagnosis of peripheral arterial disease. Foot sole temperature was correlated with the ankle-brachial index (ABI), carotid-femoral pulse wave velocity (cfPWV), brachial-ankle pulse wave velocity (baPWV), and arterial age. Methods: A total of 175 patients with type 2 diabetes mellitus, without a previous diagnosis of PAD, were recruited. Comorbidities, anthropometry, biochemical analysis results, temperature, ABI, cfPWV, baPWV, and arterial age were recorded. Forty-two temperature records were obtained from the sole of the foot with an FLIR T865 thermal imaging camera. ABI, cfPWV, baPWV, and arterial age were obtained using plethysmographic and oscillometric methods. Statistical analysis was performed with SPSS v.29.0 (correlations and multiple linear regression models). Results: All temperature points analyzed correlated negatively with ABI (p < 0.001) and rho values ranged from -0.168 to -0.210. Likewise, cfPWV, baPWV, and arterial age had similar results, since most temperature records showed low rho values and a negative correlation with these parameters. Four models were developed to explain the variables of interest. Temperature was involved in all of them. The temperature of the first toe was included in the prediction of cfPWV, baPWV, and arterial age. Conclusions: There is an inversely proportional relationship between temperature and ABI, cfPWV, baPWV, and arterial age in diabetic patients without a previous diagnosis of arterial disease. Temperature can be a predictor of these hemodynamic variables.

The roles of extracranial intravascular lesion, vasodilation-induced neural entrapment, and arteriolysis in migraine treatment

The few available studies of biopsies performed during migraine surgery have revealed intravascular changes of the occipital and superficial temporal arteries. It is not clear whether these abnormalities are purely of local origin or of systemic nature. This letter discusses possible associations between extracranial vascular alterations and vasodilatory neural entrapment. Exploration of spatial differences in vascular morphology of the involved arteries could provide further insights.

Paclitaxel alters the microvascular network in the central and peripheral nervous system of rats with chemotherapy-induced painful peripheral neuropathy.

Chemotherapy-induced peripheral neurotoxicity (CIPN), with paraesthesia, numbness, dysesthesia and neuropathic pain ranks among the most common dose-limiting toxicity of several widely used anticancer drugs. Recent studies revealed the microvascular angiogenesis as a new important actor, beside peripheral neurons, in the neurotoxicity and neuropathic pain development and chronicisation. The aim of this work is to elucidate the role of vascular alterations in CIPN. We evaluated the severity of CIPN with neurophysiological, behavioural and neuropathological analysis together with the microvascular network in central and peripheral nervous systems of rats in order to correlate the features of the CIPN and the vascular abnormalities. The vascular network was quantitatively evaluated through synchrotron radiation-based X-ray phase-contrast micro-tomography imaging, measuring four specific parameters: vascular density, vessel diameter, vessel tortuosity and branching. Rats exposed to paclitaxel and affected by a severe painful sensory axonopathy showed an increased vascular density (putative sprouting angiogenesis) in the crucial districts of the central (somatosensory cortex and lumbar spinal cord) and peripheral nervous system (lumbar dorsal root ganglia). In addition, the complexity of the vascular network and the size of neo-formed vessels were significantly decreased in specific regions. On the other hand, less significant changes were observed in rats exposed to cisplatin, affected by a painless peripheral neuropathy, suggesting a specific involvement of neo-angiogenesis in the development of severe neurotoxicity and neuropathic pain. These new ground-breaking results can shed light on new pathogenetic mechanisms and potential novel therapeutic approaches for painful-CIPN.