Pub Date : 2024-10-18DOI: 10.1016/j.mvr.2024.104755
Khiany Mathias , Richard Simon Machado , Taise Cardoso , Anita dal Bó Tiscoski , Amanda Christine da Silva Kursancew , Josiane Somariva Prophiro , Jaqueline Generoso , Fabricia Petronilho
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.
先天性免疫系统由多种免疫细胞组成，包括先天性淋巴细胞（ILCs），这些细胞根据其转录因子和细胞因子特征被分为不同的亚群。其中包括自然杀伤（NK）细胞、第 1 组 ILC、第 2 组 ILC、第 3 组 ILC 和淋巴组织诱导体（LTi）。与 T 细胞和 B 细胞不同，ILCs 不表达这些细胞上常见的多种抗原受体。虽然 ILCs 在多个系统中发挥作用，但要了解它们在大脑中的作用以及与中风等神经系统疾病的关系，还需要进一步的研究。本综述探讨了 ILCs 的一般免疫学方面，尤其侧重于它们在中枢神经系统中的作用以及缺血性中风的病理生理学。
{"title":"Innate lymphoid cells in the brain: Focus on ischemic stroke","authors":"Khiany Mathias , Richard Simon Machado , Taise Cardoso , Anita dal Bó Tiscoski , Amanda Christine da Silva Kursancew , Josiane Somariva Prophiro , Jaqueline Generoso , Fabricia Petronilho","doi":"10.1016/j.mvr.2024.104755","DOIUrl":"10.1016/j.mvr.2024.104755","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104755"},"PeriodicalIF":2.9,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1016/j.mvr.2024.104754
Maria Roslik , Yury Zharikov , Andzhela Vovkogon , Nataliya Zharova , André Pontes-Silva , Tatiana Zharikova
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.
{"title":"Aortic aneurysm: Correlations with phenotypes associated with connective tissue dysplasia","authors":"Maria Roslik , Yury Zharikov , Andzhela Vovkogon , Nataliya Zharova , André Pontes-Silva , Tatiana Zharikova","doi":"10.1016/j.mvr.2024.104754","DOIUrl":"10.1016/j.mvr.2024.104754","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104754"},"PeriodicalIF":2.9,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.mvr.2024.104753
Lutfi Ozturk , Charlotte Laclau , Carine Boulon , Marion Mangin , Etheve Braz-ma , Joel Constans , Loubna Dari , Claire Le Hello
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.
{"title":"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","authors":"Lutfi Ozturk , Charlotte Laclau , Carine Boulon , Marion Mangin , Etheve Braz-ma , Joel Constans , Loubna Dari , Claire Le Hello","doi":"10.1016/j.mvr.2024.104753","DOIUrl":"10.1016/j.mvr.2024.104753","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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, <em>p</em> < 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).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104753"},"PeriodicalIF":2.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.mvr.2024.104751
George R. Abraham , Anthony P. Davenport , Stephen P. Hoole
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.
{"title":"Short communications: Endothelin-1 in cardiac allograft vasculopathy","authors":"George R. Abraham , Anthony P. Davenport , Stephen P. Hoole","doi":"10.1016/j.mvr.2024.104751","DOIUrl":"10.1016/j.mvr.2024.104751","url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Results</h3><div>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, <em>p</em> = 0.01). ET-1 TMG was positively correlated with mean intimal thickness on both IVUS and OCT (IVUS: Kendall's tau-b = 0.254, <em>p</em> = 0.02 and OCT: Kendall's tau-b = 0.344, <em>p</em> < 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], <em>p</em> = 0.01).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104751"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.mvr.2024.104752
Lina H. Raffa , Enass H. Raffa , Álvaro S. Hervella , Lucía Ramos , Jorge Novo , José Rouco , Marcos Ortega
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.
{"title":"Computer-assisted evaluation of retinal vessel tortuosity in children with sickle cell disease without retinopathy","authors":"Lina H. Raffa , Enass H. Raffa , Álvaro S. Hervella , Lucía Ramos , Jorge Novo , José Rouco , Marcos Ortega","doi":"10.1016/j.mvr.2024.104752","DOIUrl":"10.1016/j.mvr.2024.104752","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>SCD arteries had an increased local tortuosity index compared to the controls (0.0007 ± 0.0019 vs. 0.0006 ± 0.0014, <em>p</em> = 0.019). Furthermore, the SCD patients had wider vessel caliber mainly in the arteries (14.68 ± 5.3 vs. 14.06 ± 5.3, <em>p</em> < 0.001). The SCD global tortuosity did not differ significantly from that of the controls (<em>p</em> = 0.598). The female participants had significantly reduced retinal vessel tortuosity indices compared to the male participants (<em>p</em> = 0.018).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104752"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1016/j.mvr.2024.104750
Ahmet Tas , Yaren Alan , Ali Müftüoğulları , Abdullah I.M. Haj Mohammad , Sabahattin Umman , Kim H. Parker , Murat Sezer
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.
{"title":"Coronary microvascular dysfunction and autoregulatory capacity interfere with resting Dicrotic notch morphology","authors":"Ahmet Tas , Yaren Alan , Ali Müftüoğulları , Abdullah I.M. Haj Mohammad , Sabahattin Umman , Kim H. Parker , Murat Sezer","doi":"10.1016/j.mvr.2024.104750","DOIUrl":"10.1016/j.mvr.2024.104750","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104750"},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-30DOI: 10.1016/j.mvr.2024.104749
Fredrik Iredahl , Erik Tesselaar , Hanna Jonasson , Daniel Wilhelms , Joakim Henricson
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.
背景：由于未知的绝对给药剂量和给药电流对微血管可能产生的影响（即电流诱导的血管扩张），离子透入疗法研究面临着挑战。本研究旨在探讨通过重复电流脉冲经皮离子透入疗法输送不同浓度的乙酰胆碱（ACh）如何影响微血管反应的恢复曲线：这项研究包括 15 名健康志愿者，使用偏振反射光谱仪评估了前臂皮肤六个部位对五种浓度的离子渗透乙酰胆碱（从 0.0055 mM 到 55 mM）和无菌水的微血管反应。每种浓度的离子透入疗法包括三个连续的脉冲，中间间隔 8 个恢复期：结果：电流引起的反应在低浓度 ACh 和无菌水中更为明显。通过重复脉冲，低浓度 ACh 的恢复曲线更接近于高浓度：观点：通过反复电离子导入 ACh，微血管反应会因药物浓度和给药脉冲数的不同而有所变化。这些变化可能归因于皮肤传导性和渗透性的变化。
{"title":"Concentration-dependent microvascular responses to repeated iontophoresis of acetylcholine","authors":"Fredrik Iredahl , Erik Tesselaar , Hanna Jonasson , Daniel Wilhelms , Joakim Henricson","doi":"10.1016/j.mvr.2024.104749","DOIUrl":"10.1016/j.mvr.2024.104749","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Perspective</h3><div>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.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104749"},"PeriodicalIF":2.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1016/j.mvr.2024.104748
Marzena Romanowska-Kocejko , Alicja Braczko , Agata Jędrzejewska , Marta Żarczyńska-Buchowiecka , Tomasz Kocejko , Barbara Kutryb-Zając , Marcin Hellmann
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 IRindex (r = −0.375, p < 0.05). Similarly, there was a significant inverse correlation of serum asymmetric dimethyl-L-arginine levels to both HRmax (r = −0.343, p < 0.05) and HRindex (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.
{"title":"Follow-up assessment of the microvascular function in patients with long COVID","authors":"Marzena Romanowska-Kocejko , Alicja Braczko , Agata Jędrzejewska , Marta Żarczyńska-Buchowiecka , Tomasz Kocejko , Barbara Kutryb-Zając , Marcin Hellmann","doi":"10.1016/j.mvr.2024.104748","DOIUrl":"10.1016/j.mvr.2024.104748","url":null,"abstract":"<div><p>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 (<em>n</em> = 33) and healthy controls (<em>n</em> = 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<sub>index</sub> (<em>r</em> = −0.375, <em>p</em> < 0.05). Similarly, there was a significant inverse correlation of serum asymmetric dimethyl-L-arginine levels to both HR<sub>max</sub> (<em>r</em> = −0.343, p < 0.05) and HR<sub>index</sub> (<em>r</em> = −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, <em>p</em> = 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.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104748"},"PeriodicalIF":2.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142240158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-15DOI: 10.1016/j.mvr.2024.104747
Huangdong Li , Jingyu Zhang , Xi Yin , Zheng Xiang , Wangjian Qiu , Amy Michelle Huang , Li Wang , Quan Lv , Zhiping Liu
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.
{"title":"Inter-eye asymmetry of microvascular density in patients on hydroxychloroquine therapy by optical coherence tomography angiography","authors":"Huangdong Li , Jingyu Zhang , Xi Yin , Zheng Xiang , Wangjian Qiu , Amy Michelle Huang , Li Wang , Quan Lv , Zhiping Liu","doi":"10.1016/j.mvr.2024.104747","DOIUrl":"10.1016/j.mvr.2024.104747","url":null,"abstract":"<div><h3>Aims</h3><div>To explore the inter-eye retinal microvascular density asymmetry of patients on hydroxychloroquine (HCQ) therapy through optical coherence tomography angiography (OCTA).</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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, <em>p</em> < 0.01) and pfVD of SCP (2.55 ± 1.26 vs 1.78 ± 1.06, <em>p</em> = 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, <em>p</em> < 0.01) and pfVD of SCP (AUC = 0.71, <em>p</em> = 0.02) exhibited greater discrimination power.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104747"},"PeriodicalIF":2.9,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13DOI: 10.1016/j.mvr.2024.104746
Jannis Renzelmann, Sebastian Heene, Rebecca Jonczyk, Jana Krüger, Suhayla Alnajjar, Cornelia Blume
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/cm2) 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.
{"title":"Sustainability of shear stress conditioning in endothelial colony-forming cells compared to human aortic endothelial cells to underline suitability for tissue-engineered vascular grafts","authors":"Jannis Renzelmann, Sebastian Heene, Rebecca Jonczyk, Jana Krüger, Suhayla Alnajjar, Cornelia Blume","doi":"10.1016/j.mvr.2024.104746","DOIUrl":"10.1016/j.mvr.2024.104746","url":null,"abstract":"<div><p>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<sup>2</sup>) 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.</p></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"157 ","pages":"Article 104746"},"PeriodicalIF":2.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026286224000955/pdfft?md5=fee775efdfe2befebd14889481e9b1b5&pid=1-s2.0-S0026286224000955-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142274433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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