Microvascular Research[JOURNAL]
Sun
200 papers
Cardioprotective effects of l-glutamine in an ischemic rat heart model.
Kawakami A, Sato H, Nakadate Y … +4 more , Roque P, Khoutorsky A, Matsukawa T, Schricker T
Microvasc Res · 2025 Mar · PMID 39571748 · Publisher ↗
INTRODUCTION: l-glutamine has been shown to have cardioprotective effects in models of ischemia-reperfusion injury. Its potential cardioprotective effects when given before and during early reperfusion, however, have not...
INTRODUCTION: l-glutamine has been shown to have cardioprotective effects in models of ischemia-reperfusion injury. Its potential cardioprotective effects when given before and during early reperfusion, however, have not been studied. METHODS: This study hypothesized that l-glutamine administered before and after myocardial ischemia provides better cardioprotection than when administered after ischemia only. Eighteen male rat hearts were exposed to 15 min of ischemia using the Langendorff system and randomly assigned to three groups of six each. Group one received Krebs-Henseleit (KH) buffer over 20 min before ischemia and during 20 min of reperfusion (Control), group two received KH buffer containing 2.5 mmol･L glutamine during reperfusion (Post-Gln) and group three was given KH buffer containing glutamine before and after the ischemic insult (Pre + Post-Gln). Indicators of hemodynamics such as maximum left ventricular derivative of pressure development (LV dP/dt max) were recorded at 5, 10, 15 and 20 min post-reperfusion. Myocardial levels of O-linked β-N-acetylglucosamine (O-GlcNAc) and heat shock protein 70 (HSP70) were measured by Western blotting technique after 20 min of reperfusion. RESULTS: The LV dp/dt max in the Pre + Post-Gln group was significantly elevated as compared to the Post-Gln group after 10 min of reperfusion and was significantly higher than in the control group at all-time points. Myocardial expression of O-GlcNAc was increased in the Pre + Post-Gln group (P < 0.01 vs. control) without showing any differences in HSP70. CONCLUSION: In this model of stunned myocardium, pre- and post-ischemic administration of l-glutamine improved cardiac function indicating cardioprotective effects, possibly mediated by O-GlcNAc.
Statin-treated RBC dynamics in a microfluidic porous-like network.
Stathoulopoulos A, König CS, Ramachandran S … +1 more , Balabani S
Microvasc Res · 2025 Mar · PMID 39571747 · Publisher ↗
The impact of therapeutic interventions on red blood cell (RBC) deformability and microscale transport is investigated, using statins as an exemplar. Human RBCs were treated in vitro with two commonly prescribed statins,...
The impact of therapeutic interventions on red blood cell (RBC) deformability and microscale transport is investigated, using statins as an exemplar. Human RBCs were treated in vitro with two commonly prescribed statins, atorvastatin and rosuvastatin, at clinically relevant concentrations. Changes in RBC deformability were quantified using a microfluidic-based ektacytometer and expressed in terms of the elongation index. Dilute suspensions of the statin-treated RBCs were then perfused through a microfluidic pillar array, at a constant flow rate and negligible inertia, and imaged. Particle Tracking Velocimetry (PTV) was applied to track RBCs, identify preferential paths and estimate their velocities, whereas image processing was used to estimate cell dynamics, perfusion metrics and distributions. The findings were compared against those of healthy, untreated cells. Statins enhanced RBC deformability in agreement with literature. The extent of enhancement was found to be statin-dependent. The softer statin-treated cells were found to flow in straight, less tortuous paths, spend more time inside the pillar array and exhibit lower velocities compared to healthy RBCs, attributed to their enhanced deformation and longer shape recovery time upon impact with the array posts. The in vitro microfluidic approach demonstrated here may serve as a monitoring tool to personalise and maximise the outcome of a therapeutic treatment.
Retinal vascular alterations are associated with cognitive function and neuroimaging in white matter hyperintensities.
Tao R, Wei Z, Chen X … +5 more , Wang Q, Liu X, Lu Q, Zhao J, Zhou H
Microvasc Res · 2025 Mar · PMID 39566656 · Publisher ↗
AIM: To reveal alterations in retinal structure, vessels, and function, and their association with cognitive function and neuroimaging in white matter hyperintensities (WMH). METHODS: This study enlisted WMH and age-matc...
AIM: To reveal alterations in retinal structure, vessels, and function, and their association with cognitive function and neuroimaging in white matter hyperintensities (WMH). METHODS: This 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). RESULTS: A 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. CONCLUSION: WMH 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.
A multimodal imaging approach to investigate retinal oxygen and vascular dynamics, and neural dysfunction in bietti crystalline dystrophy.
Yin S, Wang J, Zhu J … +7 more , Feng X, Zhang H, Li H, Xiu J, Zhou C, Ren Q, Wei W
Microvasc Res · 2025 Jan · PMID 39522674 · Publisher ↗
BACKGROUND: This study aimed to explore retinal changes in Bietti crystalline dystrophy (BCD) patients, including retinal metabolism, blood flow, vascular remodeling, and pupillary light reflex (PLR) abnormalities. METHO...
BACKGROUND: This study aimed to explore retinal changes in Bietti crystalline dystrophy (BCD) patients, including retinal metabolism, blood flow, vascular remodeling, and pupillary light reflex (PLR) abnormalities. METHODS: This cross-sectional study included 120 eyes from BCD patients and 120 eyes from healthy controls, utilizing a multimodal imaging system (MEFIAS 3200, SYSEYE, Chongqing, China) to evaluate retinal oxygenation, blood flow, vascular structure, and PLR. Measurements included oxygen saturation, blood flow velocity, vessel diameters, and pulsatility metrics. PLR parameters were assessed under specific light stimuli. RESULTS: BCD patients demonstrated significantly higher retinal oxygen saturation and content, but lower oxygen utilization and metabolism compared to controls, with more pronounced declines in those over 40 years old. Vascular parameters revealed smaller external diameters and larger lumen diameters, indicating vascular remodeling. Retinal blood flow was lower, while the resistivity index was higher in BCD patients. Additionally, PLR abnormalities were noted, including reduced constriction amplitude, pupil constriction ratio, constriction duration, and maximum constriction velocity, along with prolonged latency were observed in BCD patients. CONCLUSION: BCD patients had significant retinal and vascular changes, along with PLR impairments, especially in patients over 40. More targeted interventions should be focused in future research.
Increased angiopoietin-1 improves nailfold capillary morphology in patients with systemic sclerosis.
Shima Y, Watanabe A, Inoue N … +4 more , Maruyama T, Kunitomo E, Matsushima Y, Kumanogoh A
Microvasc Res · 2025 Jan · PMID 39515460 · Publisher ↗
OBJECTIVE: Raynaud's phenomenon is a common symptom of systemic sclerosis. We previously reported that elbow heating increases angiopoietin-1 in the fingertips and alleviates Raynaud's phenomenon. Angiopoietin-1 levels d...
OBJECTIVE: Raynaud's phenomenon is a common symptom of systemic sclerosis. We previously reported that elbow heating increases angiopoietin-1 in the fingertips and alleviates Raynaud's phenomenon. Angiopoietin-1 levels decrease in patients with systemic sclerosis with severe capillary damage. We aimed to conduct a prospective study to confirm whether the increase in angiopoietin-1 caused by heating modifies capillary morphology. METHODS: The left ring fingers of 19 patients with systemic sclerosis were monitored six times at 4-week intervals using capillaroscopy, during which both elbows were heated using disposable heating pads for 8 weeks. Blood samples were collected from the same fingertips four times-before heating, twice during heating, and once after heating-to measure angiopoietin-1. RESULTS: In six patients, the peak increase in angiopoietin-1 occurred 4 weeks after the start of heating, whereas in seven patients, the peak value was observed 4 weeks after the termination thereof. No change in the density of the front-row capillaries was observed by capillaroscopy. The proportion of hairpin-shaped capillaries increased from 20.2 % during the preheating period to 26.6 % during the heating period (p = 0.00107). When a correlation coefficient of 0.6 or higher was set as significant, there was a strong correlation between changes in fingertip angiopoietin-1 levels and changes in the proportion of hairpin-shaped capillaries in six patients. CONCLUSION: Increased angiopoietin-1 levels in the fingertip due to elbow heating may improve the peripheral capillary morphology in patients with systemic sclerosis.
The role of the cyclooxygenase-2 pathway in tissue ischemia and revascularization following skeletal muscle injury induced by bothropic snake venom.
Correia MR, Han SW, Escalante T … +1 more , Moreira V
Microvasc Res · 2025 Jan · PMID 39510245 · Publisher ↗
Bothrops asper venom (Bav) contains metalloproteinases that disrupt the microvascular system, impairing muscle tissue regeneration after injury. This study investigated the impact of the cyclooxygenase-2 (COX-2) pathway...
Bothrops asper venom (Bav) contains metalloproteinases that disrupt the microvascular system, impairing muscle tissue regeneration after injury. This study investigated the impact of the cyclooxygenase-2 (COX-2) pathway on vascular injury and revascularization in muscle injuries induced by Bav. Mice were injected with Bav into the gastrocnemius muscle and treated with lumiracoxib, a selective COX-2 inhibitor, 30 min, 2 days, and 6 days post-Bav injection. Muscle tissue was analyzed at 24 h, 7 days, and 21 days post-injection. A decrease in COX-2 expression at 24 h post-Bav injection indicated significant necrosis and tissue loss. Both Bav injection and lumiracoxib treatment influenced the decrease of prostaglandin (PG)D and PGE production. Seven and 21 days post-Bav injections, COX-2 expression increased, along with PGDs levels unaffected by lumiracoxib, indicating that the other isoform COX-1 pathway could contribute to the release of PGs. Bav/lumiracoxib treated animals presented exacerbated limb ischemia, implying that COX-2-derived prostaglandins preserve vessel integrity. CD31, an angiogenesis marker, initially (24 h) decreased post-Bav injection but increased at 7 and 21 days in Bav/lumiracoxib mice, suggesting a down-modulatory role for COX-2-derived prostaglandins in early angiogenesis and tissue regeneration. Vascular endothelial growth factor (VEGF) production rose 7 days post-Bav injection, supporting its role in angiogenesis. Previous treatment with lumiracoxib promoted release of VEGF levels 21 days post-Bav injury showing that the inhibition of COX-2 pathway in the early stage of revascularization stimulates the neovascularization regulated by elevated release of VEGF. Similarly, metalloproteinases (MMPs), such as MMP-9, MMP-10, and MMP-13, crucial for vascular remodeling, were elevated 21 days after Bav/lumiracoxib treatment. In conclusion, the COX-2 pathway is essential to decrease the high grade of ischemia caused by acute injury induced by Bav. However, the decrease of activity in the COX-2 pathway in the first stages of revascularization contributes to the elevated production of key pro-angiogenic mediators that up-regulate the restoration of microvasculature and blood flow in muscle tissue injured by botropic venoms.
Morphometrics of polypoidal choroidal vasculopathy lesions and choroidal vascular associated with treatment response using swept-source optical coherence tomography angiography.
Zhang Y, Wang J, Zheng Z … +3 more , Song S, Gu X, Yu X
Microvasc Res · 2025 Jan · PMID 39505235 · Publisher ↗
PURPOSE: To evaluate quantitative metrics of neovascularization lesions and choroidal vascular using swept-source optical coherence tomography angiography (SS-OCTA) in polypoidal choroidal vasculopathy (PCV) eyes, and in...
PURPOSE: To evaluate quantitative metrics of neovascularization lesions and choroidal vascular using swept-source optical coherence tomography angiography (SS-OCTA) in polypoidal choroidal vasculopathy (PCV) eyes, and investigate the relationship between imaging biomarkers and treatment outcomes of intravitreal anti-vascular endothelial growth factor (VEGF). METHODS: We retrospectively recruited 56 PCV patients. Choroidal features included subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI). Quantitative metrics of neovascularization lesions included total vessel length (TVL), average vessel length (AVL), junction density (JD), total number of endpoints (TNE), and mean lacunarity (ML). We performed multivariate logistic and linear regression models to determine the prognostic factors for functional and morphological outcomes. RESULTS: By comparison, functional good-responders had poorer best corrected visual acuity, higher TNE, and lower ML at baseline. Morphological good-responders had higher central retinal thickness, higher TNE, lower TVL and AVL, lower ML, lower SFCT and CVI. High-shrinkage of vessel area subgroup had higher JD and TNE, lower TVL and AVL, lower ML, lower SFCT and CVI. Multivariate analysis showed good morphological response was correlated with lower SFCT (P < 0.01). High-shrinkage subgroup was correlated with lower AVL (P = 0.017) and higher TNE (P < 0.01). CONCLUSION: Quantitative metrics of neovascularization lesions and choroidal characteristics using SS-OCTA had the potential to be imaging biomarkers for predicting the response to anti-VEGF treatment. PCV lesions with higher TNE and lower AVL tended to appear higher shrinkage of vessel area, and lower SFCT was correlated with good morphological response.
Dehydroepiandrosterone (DHEA), a circulating steroid hormone precursor produced potent vasorelaxation in rat aorta and mesenteric arteries through blockade of L-type voltage-dependent calcium channels.
Mishra D, Yadav P, Iqbal H … +3 more , Parashar S, Negi AS, Chanda D
Microvasc Res · 2025 Jan · PMID 39505234 · Publisher ↗
Dehydroepiandrosterone (DHEA) is known for potent cardioprotective properties and diminished DHEA level in plasma is often associated with hypertension and age-related anomalies. However, putative ex-vivo vasorelaxation...
Dehydroepiandrosterone (DHEA) is known for potent cardioprotective properties and diminished DHEA level in plasma is often associated with hypertension and age-related anomalies. However, putative ex-vivo vasorelaxation potential of DHEA in systemic resistance vessels like mesenteric arteries and conduit arteries like aorta are still to be worked out. The study aimed to explore vasorelaxation potential of DHEA in superior and resistance mesenteric arteries and aorta in rats and to determine the contribution L-type Voltage dependent calcium channel (L-VDCC) in the relaxation response in these arterial tissues. Ex-vivo vasorelaxation potential of DHEA in isolated arterial tissues were evaluated and the mechanism of vasorelaxation induced by DHEA was characterized by contraction experiment in isolated arterial tissue and in-vitro calcium imaging assay using Fluo-4 in primary vascular smooth muscle cells derived from aorta. In the current study, DHEA was found to exhibit potent concentration dependent, endothelium and potassium channel independent vasorelaxation response in conduit and resistance arteries. The block of L-type VDCCs was evident from the findings that DHEA in a concentration-dependent manner inhibited both BAY K-8644 and CaCl-induced contractions. The results of the contraction experiment were further substantiated by Fluo-4 mediated calcium imaging assay in primary rat vascular smooth muscle wherein DHEA concentration dependently blocked noradrenaline and BAY K-8644-induced rise in intracellular calcium fluorescence. The present study showed potent endothelium and potassium channel independent vasorelaxation properties of DHEA in aorta, superior and resistance mesenteric artery mediated predominantly through blockade of L-VDCC.
Characterization of microcirculatory endothelial functions in a D-Galactose-induced aging model.
Li Z, He Y, Zhang Q … +3 more , Li B, Xiu R, Zhang H
Microvasc Res · 2025 Jan · PMID 39490807 · Publisher ↗
BACKGROUND: Microcirculation health is critical to human health, and aging is an important factor affecting microcirculation health. Although D-Galactose has been widely used in aging research models, there is a lack of...
BACKGROUND: Microcirculation health is critical to human health, and aging is an important factor affecting microcirculation health. Although D-Galactose has been widely used in aging research models, there is a lack of relevant studies on D-Galactose simulating microcirculatory aging. Here, we explored microcirculatory endothelial function in D-Galactose-induced aging mice. METHODS: Intraperitoneal injection of 150 mg/(kg·d) of D-Galactose was given to cause senescence in mice. Aging was evaluated by SA-β-gal (senescence-associated β-galactosidase) staining. The auricular skin and hepatic microcirculation of mice were observed and detected by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC) and microcirculation apparatus. The aging of microcirculation was analyzed from oxidative stress, endothelial impairment, inflammation, microvascular morphology and hemodynamics. RESULTS: In aging mice, percentage of SA-β-gal positive area, oxidative stress products reactive oxygen species (ROS) and nitric oxide (NO), endothelial impairment marker syndecan-1 (SDC-1), stromal cell derived factor-1 (SDF-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in the senescence-associated secretory phenotype (SASP) were all up-regulated. The tortuosity of microvessels increased in aging mice, the linear density did not change significantly, but the total length of narrow microvessels (TLNMV) increased and wide microvessels (TLWMV) decreased, speculate that vasomotor dysfunction may be present. Hemodynamically, both perfusion and velocity of blood flow were reduced in senescent mice, presumably due to endothelial dysfunction. CONCLUSION: Microcirculatory endothelial dysfunction is induced by D-Galactose, leading to microcirculatory aging. In vivo, this is manifested by elevated levels of oxidative stress, impaired endothelial glycocalyx (eGC), and a greater production of chemokines and adhesive molecules. These changes cause vasomotor dysfunction and remodeling, ultimately leading to hemodynamic impairment.
Repeated treatment with VEGF receptor inhibitors induces phenotypic changes in endothelial cells and pericytes in the rat retina.
Nakano A, Kawada T, Morita A … +1 more , Nakahara T
Microvasc Res · 2025 Jan · PMID 39454823 · Publisher ↗
Abnormal ocular angiogenesis is a major cause of visual impairment and vision loss in neovascularization-related diseases. Currently, anti-vascular endothelial growth factor (VEGF) drugs are used to treat ocular neovascu...
Abnormal ocular angiogenesis is a major cause of visual impairment and vision loss in neovascularization-related diseases. Currently, anti-vascular endothelial growth factor (VEGF) drugs are used to treat ocular neovascularization, but repeated injections are needed to maintain their therapeutic effects. However, repeated injection of anti-VEGF drugs may affect the retinal blood vessel phenotype and diminish therapeutic effects. In this study, we aimed to investigate the phenotypic changes in endothelial cells and pericytes caused by the repeated interruption of the VEGF receptor signaling pathway in neonatal rats. KRN633 (10 mg/kg), a VEGF receptor tyrosine kinase inhibitor, was subcutaneously administered on postnatal day (P)-7 and P8 (first round), P14 and P15 (second round), and P21 and P22 (third round). The rat eyes were collected on P7, P9, P14, P16, P21, P23, P28, and P35. Using retinal flat-mount specimens stained with specific markers for vascular endothelial cells, basement membranes, and pericytes, the arteriolar tortuosity, capillary area density, and distribution of pericytes were evaluated. Significant loss of capillaries was observed the day after the first round of KRN633 treatment, after which aggressive angiogenesis occurred, leading to the formation of tortuous arterioles. Rats that completed second and third rounds of KRN633 treatment showed more severe abnormalities in the retinal vasculature than those that only completed first round treatment. Repeated treatment with KRN633 decreased the anti-angiogenic effects but increased the immunoreactivity of α-smooth muscle actin in the pericytes on veins and capillaries. α-Smooth muscle actin expression was inversely correlated to anti-angiogenic effects. Overall, these results revealed that repeated interruption of VEGF receptor signaling pathway altered the phenotypes of endothelial cells and pericytes and induced anti-VEGF drug resistance. Therefore, careful follow-up is necessary when using anti-VEGF drugs to treat abnormal angiogenesis-associated ocular diseases.
Innate lymphoid cells in the brain: Focus on ischemic stroke.
Mathias K, Machado RS, Cardoso T … +5 more , Tiscoski ADB, Kursancew ACDS, Prophiro JS, Generoso J, Petronilho F
Microvasc Res · 2025 Jan · PMID 39427988 · Publisher ↗
The innate immune system consists of a diverse set of immune cells, including innate lymphoid cells (ILCs), which are grouped into subsets based on their transcription factors and cytokine profiles. Among these are natur...
The innate immune system consists of a diverse set of immune cells, including innate lymphoid cells (ILCs), which are grouped into subsets based on their transcription factors and cytokine profiles. Among these are natural killer (NK) cells, group 1 ILCs, group 2 ILCs, group 3 ILCs, and lymphoid tissue inducers (LTi). Unlike T and B cells, ILCs do not express the diverse antigen receptors typically found on those cells. Although ILCs function in various systems, further research is needed to understand their role in the brain and their involvement in neurological diseases such as stroke. This review explores the general immunological aspects of ILCs, with a particular focus on their role in the central nervous system and the pathophysiology of ischemic stroke.
Aortic aneurysm: Correlations with phenotypes associated with connective tissue dysplasia.
Roslik M, Zharikov Y, Vovkogon A … +3 more , Zharova N, Pontes-Silva A, Zharikova T
Microvasc Res · 2025 Jan · PMID 39401669 · Publisher ↗
An aortic aneurysm is a localized enlargement that exceeds the normal diameter of the vessel by 50 %, posing a risk due to the likelihood of rupture. The cause of aortic aneurysm, especially in young people, is connectiv...
An aortic aneurysm is a localized enlargement that exceeds the normal diameter of the vessel by 50 %, posing a risk due to the likelihood of rupture. The cause of aortic aneurysm, especially in young people, is connective tissue dysplasia, a condition characterized by defects in the assembly of collagen and elastin proteins, leading to changes in elastic properties and disruption of the formation of organs and their systems. The article presents data confirming the relationship between many morphological manifestations of connective tissue dysplasia (e.g., funnel-shaped deformation of the sternum, scoliosis of the thoracic spine, abdominal hernias, arterial tortuosity, striae of atypical localization) and the risk of aortic aneurysm formation. The literature suggests that the identified combinations of some external manifestations of connective tissue dysplasia deserve special attention and may be constitutional markers for the possible development of aortic aneurysm, which is a promising direction for further research in this area.
Analysis of nailfold capillaroscopy images with artificial intelligence: Data from literature and performance of machine learning and deep learning from images acquired in the SCLEROCAP study.
Ozturk L, Laclau C, Boulon C … +5 more , Mangin M, Braz-Ma E, Constans J, Dari L, Le Hello C
Microvasc Res · 2025 Jan · PMID 39389419 · Publisher ↗
OBJECTIVE: To evaluate the performance of machine learning and then deep learning to detect a systemic scleroderma (SSc) landscape from the same set of nailfold capillaroscopy (NC) images from the French prospective mult...
OBJECTIVE: To evaluate the performance of machine learning and then deep learning to detect a systemic scleroderma (SSc) landscape from the same set of nailfold capillaroscopy (NC) images from the French prospective multicenter observational study SCLEROCAP. METHODS: NC images from the first 100 SCLEROCAP patients were analyzed to assess the performance of machine learning and then deep learning in identifying the SSc landscape, the NC images having previously been independently and consensually labeled by expert clinicians. Images were divided into a training set (70 %) and a validation set (30 %). After features extraction from the NC images, we tested six classifiers (random forests (RF), support vector machine (SVM), logistic regression (LR), light gradient boosting (LGB), extreme gradient boosting (XGB), K-nearest neighbors (KNN)) on the training set with five different combinations of the images. The performance of each classifier was evaluated by the F1 score. In the deep learning section, we tested three pre-trained models from the TIMM library (ResNet-18, DenseNet-121 and VGG-16) on raw NC images after applying image augmentation methods. RESULTS: With machine learning, performance ranged from 0.60 to 0.73 for each variable, with Hu and Haralick moments being the most discriminating. Performance was highest with the RF, LGB and XGB models (F1 scores: 0.75-0.79). The highest score was obtained by combining all variables and using the LGB model (F1 score: 0.79 ± 0.05, p < 0.01). With deep learning, performance reached a minimum accuracy of 0.87. The best results were obtained with the DenseNet-121 model (accuracy 0.94 ± 0.02, F1 score 0.94 ± 0.02, AUC 0.95 ± 0.03) as compared to ResNet-18 (accuracy 0.87 ± 0.04, F1 score 0.85 ± 0.03, AUC 0.87 ± 0.04) and VGG-16 (accuracy 0.90 ± 0.03, F1 score 0.91 ± 0.02, AUC 0.91 ± 0.04). CONCLUSION: By using machine learning and then deep learning on the same set of labeled NC images from the SCLEROCAP study, the highest performances to detect SSc landscape were obtained with deep learning and in particular DenseNet-121. This pre-trained model could therefore be used to automatically interpret NC images in case of suspected SSc. This result nevertheless needs to be confirmed on a larger number of NC images.
Computer-assisted evaluation of retinal vessel tortuosity in children with sickle cell disease without retinopathy.
Raffa LH, Raffa EH, Hervella ÁS … +4 more , Ramos L, Novo J, Rouco J, Ortega M
Microvasc Res · 2025 Jan · PMID 39362484 · Publisher ↗
OBJECTIVE: We assessed the predictive efficacy of automatically quantified retinal vascular tortuosity from the fundus pictures of patients with sickle cell disease (SCD) without evident retinopathy. METHODS: Retinal ima...
OBJECTIVE: We assessed the predictive efficacy of automatically quantified retinal vascular tortuosity from the fundus pictures of patients with sickle cell disease (SCD) without evident retinopathy. METHODS: Retinal images were obtained from 31 healthy and 31 SCD participants using fundus imaging and analyzed using a novel computational automated metric assessment. The local and global vessel tortuosity and their relationship with systemic disease parameters were analyzed based on the images. RESULTS: SCD arteries had an increased local tortuosity index compared to the controls (0.0007 ± 0.0019 vs. 0.0006 ± 0.0014, p = 0.019). Furthermore, the SCD patients had wider vessel caliber mainly in the arteries (14.68 ± 5.3 vs. 14.06 ± 5.3, p < 0.001). The SCD global tortuosity did not differ significantly from that of the controls (p = 0.598). The female participants had significantly reduced retinal vessel tortuosity indices compared to the male participants (p = 0.018). CONCLUSION: Retinal arterial tortuosity and caliber were reliable and objective measures that could be used as a non-invasive prognostic and diagnostic indicator in sickle cell retinopathy. Further studies are required to correlate these local vascular parameters to systemic risk factors and monitor their progression and change over time.
Short communications: Endothelin-1 in cardiac allograft vasculopathy.
Abraham GR, Davenport AP, Hoole SP
Microvasc Res · 2025 Jan · PMID 39362483 · Publisher ↗
INTRODUCTION: Cardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplant. Endothelin-1 (ET-1) is a highly potent vasoconstrictor peptide derived from the vascular endothelium with multipl...
INTRODUCTION: Cardiac allograft vasculopathy (CAV) is a leading cause of death following heart transplant. Endothelin-1 (ET-1) is a highly potent vasoconstrictor peptide derived from the vascular endothelium with multiple biological actions known to be relevant for CAV. We assessed the trans-myocardial gradient (TMG: coronary sinus minus coronary artery concentration: negative = extraction, positive = secretion) of ET-1 in heart transplant patients to determine correlations with angiographic, Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) features of CAV. RESULTS: Vessels with more severe CAV demonstrated significantly higher (more positive) ET-1 TMG (IVUS Stanford Grade IV: -0.05 [-0.21, 0.13] pg/ml versus Stanford Grade I-III: -0.31 [-0.64, -0.11] pg/ml, p = 0.01). ET-1 TMG was positively correlated with mean intimal thickness on both IVUS and OCT (IVUS: Kendall's tau-b = 0.254, p = 0.02 and OCT: Kendall's tau-b = 0.344, p < 0.0001). Patients who died had net ET-1 release compared with surviving patients (died: 0.21 [0.19-0.24] versus surviving: -0.28 [-0.52, -0.17], p = 0.01). CONCLUSION: In heart transplant patients, coronary arteries with more intimal thickening are associated with a higher (more positive) trans-myocardial gradient of ET-1, suggesting that up-regulated ET-1 release in the coronary circulation may be permissive for the development of CAV.
Coronary microvascular dysfunction and autoregulatory capacity interfere with resting Dicrotic notch morphology.
Tas A, Alan Y, Müftüoğulları A … +4 more , Haj Mohammad AIM, Umman S, Parker KH, Sezer M
Microvasc Res · 2025 Jan · PMID 39357645 · Publisher ↗
Coronary microvascular vasodilator capacity is substantially associated with coronary pressure waveform and dicrotic notch morphology, with or without concomitant epicardial disease. A prominent dicrotic notch is associa...
Coronary microvascular vasodilator capacity is substantially associated with coronary pressure waveform and dicrotic notch morphology, with or without concomitant epicardial disease. A prominent dicrotic notch is associated with preserved microvascular vasodilatory capacity and adequate resting microvascular tonus without relative hyperaemic state, cumulatively indicating a better microcirculatory health.
Concentration-dependent microvascular responses to repeated iontophoresis of acetylcholine.
Iredahl F, Tesselaar E, Jonasson H … +2 more , Wilhelms D, Henricson J
Microvasc Res · 2025 Jan · PMID 39357644 · Publisher ↗
BACKGROUND: Iontophoresis studies face challenges due to the unknown absolute drug dose delivered and the possible effect of the current used in drug delivery on the microvessels, known as current-induced vasodilation. T...
BACKGROUND: Iontophoresis studies face challenges due to the unknown absolute drug dose delivered and the possible effect of the current used in drug delivery on the microvessels, known as current-induced vasodilation. This study aimed to investigate how various concentrations of acetylcholine (ACh), delivered through transdermal iontophoresis using repeated current pulses, impact the recovery profile of the microvascular response. METHODS: The study included fifteen healthy volunteers, and microvascular responses to five concentrations of iontophorised ACh (ranging from 0.0055 mM to 55 mM) and sterile water were assessed at six forearm skin sites using polarized reflectance spectroscopy. Iontophoresis at each concentration involved three consecutive pulses separated 8 recovery periods. RESULTS: Current-induced responses were more pronounced for lower concentrations of ACh and for sterile water. With repeated pulses, lower concentrations of ACh exhibited a recovery profile more akin to higher concentrations. PERSPECTIVE: Through repeated iontophoresis of ACh, microvascular responses exhibit variation based on the drug concentration and the number of pulses administered. These variations are likely attributed to changes in skin conductivity and permeability.
Follow-up assessment of the microvascular function in patients with long COVID.
Romanowska-Kocejko M, Braczko A, Jędrzejewska A … +4 more , Żarczyńska-Buchowiecka M, Kocejko T, Kutryb-Zając B, Hellmann M
Microvasc Res · 2025 Jan · PMID 39293561 · Publisher ↗
Long COVID is a complex pathophysiological condition. However, accumulating data suggests that COVID-19 is a systemic microvascular endothelial dysfunction with different clinical manifestations. In this study, a microva...
Long COVID is a complex pathophysiological condition. However, accumulating data suggests that COVID-19 is a systemic microvascular endothelial dysfunction with different clinical manifestations. In this study, a microvascular function was assessed in long COVID patients (n = 33) and healthy controls (n = 30) using flow-mediated skin fluorescence technique (FMSF), based on measurements of nicotinamide adenine dinucleotide fluorescence intensity during brachial artery occlusion (ischemic response, IR) and immediately after occlusion (hyperemic response, HR). Microcirculatory function readings were taken twice, 3 months apart. In addition, we quantified biochemical markers such as the serum L-arginine derivatives and hypoxia-inducible factor 1α (HIF1α) to assess their relation with microvascular parameters evaluated in vivo. In patients with long COVID, serum HIF1α was significantly correlated to IR (r = -0.375, p < 0.05). Similarly, there was a significant inverse correlation of serum asymmetric dimethyl-L-arginine levels to both HR (r = -0.343, p < 0.05) and HR (r = -0.335, p < 0.05). The IR parameters were found lower or negative in long COVID patients and recovered in three-month follow-up. Hypoxia sensitivity value was significantly higher in long COVID patients examined after three months of treatment based on the combination of ACE-inhibitors and beta-adrenolytic compared to baseline condition (85.2 ± 73.8 vs. 39.9 ± 51.7 respectively, p = 0.009). This study provides evidence that FMSF is a sensitive, non-invasive technique to track changes in microvascular function that was impaired in long COVID and recovered after 3 months, especially in patients receiving a cardioprotective therapy.
Inter-eye asymmetry of microvascular density in patients on hydroxychloroquine therapy by optical coherence tomography angiography.
Li H, Zhang J, Yin X … +6 more , Xiang Z, Qiu W, Huang AM, Wang L, Lv Q, Liu Z
Microvasc Res · 2025 Jan · PMID 39288847 · Publisher ↗
AIMS: To explore the inter-eye retinal microvascular density asymmetry of patients on hydroxychloroquine (HCQ) therapy through optical coherence tomography angiography (OCTA). METHODS: 40 subjects were enrolled in this c...
AIMS: To explore the inter-eye retinal microvascular density asymmetry of patients on hydroxychloroquine (HCQ) therapy through optical coherence tomography angiography (OCTA). METHODS: 40 subjects were enrolled in this cross-sectional study, including 20 systemic lupus erythematasus patients currently treated with HCQ (40 eyes) and 20 age- and sex-matched normal controls (NCs, 40 eyes). OCTA images were obtained to measure macular and peripapillary mircrovasculatures and microstructures, including vessel density, retinal nerver fiber layer thickness, and peripapillary ganglion cell-inner plexiform layer thickness. The absolute values of the difference between right and left eyes were taken as a measure of inter-eye asymmetry. RESULTS: Macular whole image vessel density (wiVD-M) and perifoveal vessel density (pfVD) of superficial capillary plexus (SCP) were notably reduced in both the right and left eyes of the HCQ treatment group compared with NCs. Specifically, SLE patients treated with HCQ have higher inter-eye asymmetry of wiVD-M of SCP (2.28 ± 1.03 vs 1.27 ± 0.79, p < 0.01) and pfVD of SCP (2.55 ± 1.26 vs 1.78 ± 1.06, p = 0.04) compared with NCs. There were no significant differences in inter-eye asymmetry of structure parameters. Inter-eye asymmetry of wiVD-M of SCP (AUC = 0.80, p < 0.01) and pfVD of SCP (AUC = 0.71, p = 0.02) exhibited greater discrimination power. CONCLUSION: SLE Patients treated with HCQ exhibited a notably higher inter-eye vessel density asymmetry compared to that of NCs. Thus, inter-eye vessel density asymmetry could be used to screen for HCQ retinal toxicity.
Sustainability of shear stress conditioning in endothelial colony-forming cells compared to human aortic endothelial cells to underline suitability for tissue-engineered vascular grafts.
Renzelmann J, Heene S, Jonczyk R … +3 more , Krüger J, Alnajjar S, Blume C
Microvasc Res · 2025 Jan · PMID 39278537 · Publisher ↗
The endothelialization of cardiovascular implants is supposed to improve the long-term patency of these implants. In addition, in previous studies, it has been shown, that the conditioning of endothelial cells by dynamic...
The endothelialization of cardiovascular implants is supposed to improve the long-term patency of these implants. In addition, in previous studies, it has been shown, that the conditioning of endothelial cells by dynamic cultivation leads to the expression of an anti-thrombogenic phenotype. For the creation of a tissue-engineered vascular graft (TEVG), these two strategies were combined to achieve optimal hemocompatibility. In a clinical setup, this would require the transfer of the already endothelialized construct from the conditioning bioreactor to the patient. Therefore, the reversibility of the dynamic conditioning of the endothelial cells with arterial-like high shear stress (20 dyn/cm) was investigated to define the timeframe (tested in a range of up to 24 h) for the perseverance of dynamically induced phenotypical changes. Two types of endothelial cells were compared: endothelial colony-forming cells (ECFCs) and human aortic endothelial cells (HAECs). The results showed that ECFCs respond far more sensitively and rapidly to flow than HAECs. The resulting cell alignment and increased protein expression of KLF-2, Notch-4, Thrombomodulin, Tie2 and eNOS monomer was paralleled by increased eNOS and unaltered KLF-2 mRNA levels even under stopped-flow conditions. VCAM-1 mRNA and protein expression was downregulated under flow and did not recover under stopped flow. From these time kinetic results, we concluded, that the maximum time gap between the TEVG cultivated with autologous ECFCs in future reactor cultivations and the transfer to the potential TEVG recipient should be limited to ∼6 h.
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