Pub Date : 2025-03-21DOI: 10.1016/j.mvr.2025.104806
Domenico Ribatti
The chick embryo chorioallantoic membrane (CAM) has been used as an experimental in vivo model to study angiogenesis and anti-angiogenesis. Moreover, due to the lack of a fully developed immunocompetent system, the CAM is suitable to study various aspects of tumor angiogenesis and metastatic potential. In this article, we emphasize the important role of the CAM also in the study of lymphangiogenesis and tumor lymphangiogenesis in vivo. This experimental model is more advantageous than other assays because it is a relatively simple, quick, and low-cost. Finally, it does not require administrative procedures to obtain ethics committee approval for animal experimentation.
{"title":"Lymphatics in the chick embryo chorioallantoic membrane","authors":"Domenico Ribatti","doi":"10.1016/j.mvr.2025.104806","DOIUrl":"10.1016/j.mvr.2025.104806","url":null,"abstract":"<div><div>The chick embryo chorioallantoic membrane (CAM) has been used as an experimental <em>in vivo</em> model to study angiogenesis and anti-angiogenesis. Moreover, due to the lack of a fully developed immunocompetent system, the CAM is suitable to study various aspects of tumor angiogenesis and metastatic potential. In this article, we emphasize the important role of the CAM also in the study of lymphangiogenesis and tumor lymphangiogenesis <em>in vivo</em>. This experimental model is more advantageous than other assays because it is a relatively simple, quick, and low-cost. Finally, it does not require administrative procedures to obtain ethics committee approval for animal experimentation.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104806"},"PeriodicalIF":2.9,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143680560","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}
On-pump coronary artery bypass grafting (CABG) triggers inflammatory responses as a result of surgical stress and extracorporeal circulation, which affect platelet and leukocyte activation while enhancing their intimate crosstalk. Given this, the study presented here aimed to investigate platelet-T cell interaction after CABG focusing on the changes in immunomodulatory subtypes of regulatory T Cells.
Methods
Blood samples were obtained from twenty patients undergoing on-pump CABG at 5 different time points of 24 h before, immediately, 2 h, 24 h, and one week after surgery. Total leukocyte and lymphocyte counts were determined using an automatic cell counter. Platelet P-selectin expression, frequencies of CD4+ and CD8+ T cells, platelet-T cell aggregates (PTCAs), and regulatory T cells derived from CD4+ (T4reg) and CD8+ (T8reg) cells, were assessed by flow cytometry.
Results
A significant increase in total leukocyte count occurred immediately after CABG, whereas, conversely, lymphocyte and CD4+ T cells but not CD8+ T cells decreased 2 h after surgery. However, all these changes returned to pre-CABG baseline levels within a week. Platelet P-selectin expression increased immediately after surgery, followed by a two-hour delay after PTCA, and both returned to baseline after one week. T4regs and T8regs showed a similar increase and decrease trend, where T8regs but not T4regs returned to baseline one week after surgery.
Conclusion
CABG surgery induces an inflammatory response that activates platelets and enhances P-selectin expression, facilitating PTCA formation. This mechanism is critical for the dynamics and differentiation of T cells, which play an essential role in post-CABG modulation of immune responses.
{"title":"Interplay between platelet and T lymphocyte after coronary artery bypass grafting (CABG): Evidence for platelet mediated post-CABG immunomodulation","authors":"Fateme Farhid , Ehteramolsadat Hosseini , Faranak Kargar , Mehran Ghasemzadeh","doi":"10.1016/j.mvr.2025.104805","DOIUrl":"10.1016/j.mvr.2025.104805","url":null,"abstract":"<div><h3>Background</h3><div>On-pump coronary artery bypass grafting (CABG) triggers inflammatory responses as a result of surgical stress and extracorporeal circulation, which affect platelet and leukocyte activation while enhancing their intimate crosstalk. Given this, the study presented here aimed to investigate platelet-T cell interaction after CABG focusing on the changes in immunomodulatory subtypes of regulatory T Cells.</div></div><div><h3>Methods</h3><div>Blood samples were obtained from twenty patients undergoing on-pump CABG at 5 different time points of 24 h before, immediately, 2 h, 24 h, and one week after surgery. Total leukocyte and lymphocyte counts were determined using an automatic cell counter. Platelet P-selectin expression, frequencies of CD4<sup>+</sup> and CD8<sup>+</sup> T cells, platelet-T cell aggregates (PTCAs), and regulatory T cells derived from CD4<sup>+</sup> (T4reg) and CD8<sup>+</sup> (T8reg) cells, were assessed by flow cytometry.</div></div><div><h3>Results</h3><div>A significant increase in total leukocyte count occurred immediately after CABG, whereas, conversely, lymphocyte and CD4<sup>+</sup> T cells but not CD8<sup>+</sup> T cells decreased 2 h after surgery. However, all these changes returned to pre-CABG baseline levels within a week. Platelet P-selectin expression increased immediately after surgery, followed by a two-hour delay after PTCA, and both returned to baseline after one week. T4regs and T8regs showed a similar increase and decrease trend, where T8regs but not T4regs returned to baseline one week after surgery.</div></div><div><h3>Conclusion</h3><div>CABG surgery induces an inflammatory response that activates platelets and enhances P-selectin expression, facilitating PTCA formation. This mechanism is critical for the dynamics and differentiation of T cells, which play an essential role in post-CABG modulation of immune responses.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"160 ","pages":"Article 104805"},"PeriodicalIF":2.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663748","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 : 2025-02-24DOI: 10.1016/j.mvr.2025.104797
Fadia Mayyas
Background
Atherosclerotic cardiovascular diseases (ASCVDs) represent a global health burden contributing to substantial morbidity and mortality. The neutrophil gelatinase-associated lipocalin (NGAL), a small glycoprotein, is secreted by inflammatory neutrophils, macrophages, and dendritic cells, playing a role in inflammation. However, its relevance as a predictor of ASCVDs risk across patients from low to very high-risk, and correlation with the need for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) remains largely unexplored. Our objective was to assess plasma NGAl levels in patients with low to very high risk of ASCVD and their relationship with the severity of CAD and the requirement for revascularization.
Methods
Outpatients and patients undergoing catheterization were categorized into low, moderate, high, and very high risk of ASCVD. Plasma levels of NGAL were measured using ELISA and analyzed in relation to CAD status and the need for revascularization by PCI or CABG.
Results
Plasma NGAl levels were elevated in CAD patients, with higher levels in patients with acute coronary syndrome compared to those with stable angina. A gradual increase in plasma NGAl levels was noted with the elevated risk of ASCVD and degree of coronary artery stenosis. Notably, plasma NGAl level was independently correlated with ASCVD risk and the need for revascularization by PCI.
Conclusion
Our study indicates that plasma NGAl levels are linked to the risk of ASCVD and may help predict the development and severity of CAD. Further research targeting NGAL could explore its potential to mitigate the risk of ASCVD.
{"title":"Plasma neutrophil gelatinase-associated lipocalin level as a predictor of atherosclerotic cardiovascular disease risk in patients undergoing catheterization","authors":"Fadia Mayyas","doi":"10.1016/j.mvr.2025.104797","DOIUrl":"10.1016/j.mvr.2025.104797","url":null,"abstract":"<div><h3>Background</h3><div>Atherosclerotic cardiovascular diseases (ASCVDs) represent a global health burden contributing to substantial morbidity and mortality. The neutrophil gelatinase-associated lipocalin (NGAL), a small glycoprotein, is secreted by inflammatory neutrophils, macrophages, and dendritic cells, playing a role in inflammation. However, its relevance as a predictor of ASCVDs risk across patients from low to very high-risk, and correlation with the need for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) remains largely unexplored. Our objective was to assess plasma NGAl levels in patients with low to very high risk of ASCVD and their relationship with the severity of CAD and the requirement for revascularization.</div></div><div><h3>Methods</h3><div>Outpatients and patients undergoing catheterization were categorized into low, moderate, high, and very high risk of ASCVD. Plasma levels of NGAL were measured using ELISA and analyzed in relation to CAD status and the need for revascularization by PCI or CABG.</div></div><div><h3>Results</h3><div>Plasma NGAl levels were elevated in CAD patients, with higher levels in patients with acute coronary syndrome compared to those with stable angina. A gradual increase in plasma NGAl levels was noted with the elevated risk of ASCVD and degree of coronary artery stenosis. Notably, plasma NGAl level was independently correlated with ASCVD risk and the need for revascularization by PCI.</div></div><div><h3>Conclusion</h3><div>Our study indicates that plasma NGAl levels are linked to the risk of ASCVD and may help predict the development and severity of CAD. Further research targeting NGAL could explore its potential to mitigate the risk of ASCVD.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"159 ","pages":"Article 104797"},"PeriodicalIF":2.9,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143516123","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 : 2025-02-15DOI: 10.1016/j.mvr.2025.104796
S. Wilkinson , J. Wilkinson , A. Grace , D. Lyon , M. Mellor , T. Yunus , J. Manning , G. Dinsdale , M. Berks , S. Knight , N. Bakerly , A. Gebril , P. Dark , A. Herrick , C. Taylor , M. Dickinson , A. Murray
Objectives
It is understood that microvascular dysfunction plays a key role in the pathogenesis of SARS-CoV-2 coronavirus disease (COVID-19). The aim of this study was to evaluate the usefulness of an automated, quantitative nailfold capillaroscopy system in identifying microvascular changes in those confirmed with or having had COVID-19.
Methods
Ninety-seven participants were enrolled into this study and grouped as follows: 52 participants with acute COVID-19 (further grouped by disease severity) and 45 participants with convalescent COVID-19 (further grouped into long COVID i.e. symptoms beyond 12 weeks, and fully recovered). Nailfold capillaroscopy images were obtained from the bilateral ring fingers using a Dino-Lite CapillaryScope 200 Pro, a small USB handheld microscope. Images were assessed quantitatively using bespoke automated measurement software and the number of haemorrhages noted for each participant.
Results
Capillaries were predominantly ‘normal’ in appearance with narrow capillary loops and evenly distributed, but with an increased number of haemorrhages (40 % in the convalescent group and 17 % in the acute group, p=0.007). There was no statistically significant difference in the mean width of capillaries (20.9–21.8 μm) or vessel density (9.6–9.9 caps/mm; acute and convalescent group, respectively).
Conclusions
This study has demonstrated the feasibility of nailfold capillaroscopy at the critical care bedside. Capillary structure appeared normal across all groups of individuals affected by COVID-19. Although the small differences in the microvasculature in recovered patients compared to in acutely unwell patients may suggest delayed structural change due to COVID-19, these differences are unlikely to be clinically relevant. Longitudinal studies would be required to explore this in more detail.
{"title":"Imaging the microvasculature using nailfold capillaroscopy in patients with coronavirus disease-2019; A cross-sectional study","authors":"S. Wilkinson , J. Wilkinson , A. Grace , D. Lyon , M. Mellor , T. Yunus , J. Manning , G. Dinsdale , M. Berks , S. Knight , N. Bakerly , A. Gebril , P. Dark , A. Herrick , C. Taylor , M. Dickinson , A. Murray","doi":"10.1016/j.mvr.2025.104796","DOIUrl":"10.1016/j.mvr.2025.104796","url":null,"abstract":"<div><h3>Objectives</h3><div>It is understood that microvascular dysfunction plays a key role in the pathogenesis of SARS-CoV-2 coronavirus disease (COVID-19). The aim of this study was to evaluate the usefulness of an automated, quantitative nailfold capillaroscopy system in identifying microvascular changes in those confirmed with or having had COVID-19.</div></div><div><h3>Methods</h3><div>Ninety-seven participants were enrolled into this study and grouped as follows: 52 participants with acute COVID-19 (further grouped by disease severity) and 45 participants with convalescent COVID-19 (further grouped into long COVID i.e. symptoms beyond 12 weeks, and fully recovered). Nailfold capillaroscopy images were obtained from the bilateral ring fingers using a Dino-Lite CapillaryScope 200 Pro, a small USB handheld microscope. Images were assessed quantitatively using bespoke automated measurement software and the number of haemorrhages noted for each participant.</div></div><div><h3>Results</h3><div>Capillaries were predominantly ‘normal’ in appearance with narrow capillary loops and evenly distributed, but with an increased number of haemorrhages (40 % in the convalescent group and 17 % in the acute group, <em>p</em> <em>=</em> <em>0.007</em>). There was no statistically significant difference in the mean width of capillaries (20.9–21.8 μm) or vessel density (9.6–9.9 caps/mm; acute and convalescent group, respectively).</div></div><div><h3>Conclusions</h3><div>This study has demonstrated the feasibility of nailfold capillaroscopy at the critical care bedside. Capillary structure appeared normal across all groups of individuals affected by COVID-19. Although the small differences in the microvasculature in recovered patients compared to in acutely unwell patients may suggest delayed structural change due to COVID-19, these differences are unlikely to be clinically relevant. Longitudinal studies would be required to explore this in more detail.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"159 ","pages":"Article 104796"},"PeriodicalIF":2.9,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441369","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}
Prolonged sitting can impair physiological functions. We hypothesized that prolonged sitting attenuates forearm cutaneous vascular function but alternating local skin cooling and heating mitigates this attenuation. Eleven young adults (five women) sat for 75 min in thermoneutral condition (25 °C) during which skin temperature at four forearm skin sites was modulated: 1) maintained at 33 °C (control), 2) reduced to 15 °C for 4 min, then rised to 40 °C, repeated 5 times, 3) maintained at 33 °C for 4 min, then rised to 40 °C for 4 min, repeated 5 times or 4) elevated to 40 °C. Before and after 75-min prolonged sitting, venoarteriolar reflex (VAR) was assessed by a reduction in cutaneous blood flow (laser Doppler flowmetry) mediated by venous occlusion, whereas post-occlusive reactive hyperemia (PORH) was assessed by increases in cutaneous blood flow following arterial occlusion. After prolonged sitting, PORH decreased at the control (mean with 95%CI: 40.2 [34.5, 45.9] %max vs. 26.3 [19.3, 33.3] %max P < 0.001), but this response was not seen at the site subjected to alternating 15 °C cooling and 40 °C heating (P = 0.983). VAR remained unchanged before and after prolonged sitting at the control (P = 0.990), but increased with 15 °C cooling and 40 °C heating (−47.8 [−61.6, −34.1] %baseline vs. -68.0 [−75.3, −60.7] %baseline P = 0.029). We show that prolonged sitting decreases forearm cutaneous vasodilation function (PORH), but this response is mitigated by alternating local skin cooling and heating. Additionally, prolonged sitting does not affect forearm cutaneous VAR, but alternating local skin cooling and heating enhances VAR.
{"title":"Alternate local skin cooling and heating ameliorates impaired forearm skin vasodilation function mediated by prolonged sitting","authors":"Yudai Tomita , Kaname Tagawa , Takeshi Nishiyasu , Naoto Fujii","doi":"10.1016/j.mvr.2025.104795","DOIUrl":"10.1016/j.mvr.2025.104795","url":null,"abstract":"<div><div>Prolonged sitting can impair physiological functions. We hypothesized that prolonged sitting attenuates forearm cutaneous vascular function but alternating local skin cooling and heating mitigates this attenuation. Eleven young adults (five women) sat for 75 min in thermoneutral condition (25 °C) during which skin temperature at four forearm skin sites was modulated: 1) maintained at 33 °C (control), 2) reduced to 15 °C for 4 min, then rised to 40 °C, repeated 5 times, 3) maintained at 33 °C for 4 min, then rised to 40 °C for 4 min, repeated 5 times or 4) elevated to 40 °C. Before and after 75-min prolonged sitting, venoarteriolar reflex (VAR) was assessed by a reduction in cutaneous blood flow (laser Doppler flowmetry) mediated by venous occlusion, whereas post-occlusive reactive hyperemia (PORH) was assessed by increases in cutaneous blood flow following arterial occlusion. After prolonged sitting, PORH decreased at the control (mean with 95%CI: 40.2 [34.5, 45.9] %max vs. 26.3 [19.3, 33.3] %max <em>P</em> < 0.001), but this response was not seen at the site subjected to alternating 15 °C cooling and 40 °C heating (<em>P</em> = 0.983). VAR remained unchanged before and after prolonged sitting at the control (<em>P</em> = 0.990), but increased with 15 °C cooling and 40 °C heating (−47.8 [−61.6, −34.1] %baseline vs. -68.0 [−75.3, −60.7] %baseline <em>P</em> = 0.029). We show that prolonged sitting decreases forearm cutaneous vasodilation function (PORH), but this response is mitigated by alternating local skin cooling and heating. Additionally, prolonged sitting does not affect forearm cutaneous VAR, but alternating local skin cooling and heating enhances VAR.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"159 ","pages":"Article 104795"},"PeriodicalIF":2.9,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425477","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 : 2025-02-10DOI: 10.1016/j.mvr.2025.104793
Xiaoyu Dong , Yu Zou , Xiaohui Li , Na Su , Yuchen Wen , Jiale Fang , Xianqi Li , Qiang Chen , Junhong Wang
Purpose
To compare structural and vascular differences in the macular region of the retina using optical coherence tomography (OCT)/OCT angiography (OCTA) between coronary angiography (CAG)-confirmed coronary heart disease (CHD) patients and non-CHD individuals.
Methods
The study included 340 eyes from 180 CHD patients and 136 eyes from 68 controls. Imaging was conducted using the AngioVue OCT device with a macula-centered 6 mm ∗ 6 mm field of view. Retinal thickness and 2D/3D vascular-related biomarkers were derived using existing retinal layer segmentation software, and our previously proposed 2D/3D vascular and 3D foveal avascular zone segmentation methods. Statistical analyses included t-tests, Mann-Whitney U tests, chi-square tests, and Pearson's correlation.
Results
The CHD group exhibited significantly lower retinal nerve fiber layer (RNFL) thickness (r = −0.20, P < 0.001) in the inner inferior (I) region, based on macular region layer segmentation. For the 3D OCT images, as defined by the ETDRS grid, both the inner and outer retina layers in the outer superior (out-S) region were significantly thinner in the CHD group. The CHD group showed significantly lower overall 2D fractal dimension (FD) (1.72 ± 0.03 vs. 1.73 ± 0.02, P < 0.001) and vessel skeleton density (VSD) (26.61 ± 4.52 vs. 28.50 ± 3.40, P < 0.001) compared to the control group. The proposed 3D vascular density (VD) feature showed a significant difference between the groups (19.23 ± 5.67 vs. 20.69 ± 5.15, P = 0.048).
Conclusion
Thinning of retinal thickness and reduced vascular density are associated with CHD and may serve as valuable, cost-effective biomarkers for assessing coronary artery disease assessment.
目的利用光学相干断层扫描(OCT)/OCT血管造影（OCTA）技术比较冠心病（冠心病）患者与非冠心病患者视网膜黄斑区结构和血管的差异。方法采用180例冠心病患者340只眼和68例对照组136只眼。成像采用以黄斑为中心的6mm * 6mm视场的AngioVue OCT装置。视网膜厚度和2D/3D血管相关生物标志物使用现有的视网膜层分割软件，以及我们之前提出的2D/3D血管和3D中央凹无血管区分割方法。统计分析包括t检验、Mann-Whitney U检验、卡方检验和Pearson相关检验。结果冠心病组视网膜神经纤维层（RNFL）厚度显著降低(r = - 0.20, P <；0.001)，基于黄斑区域层分割。在3D OCT图像中，根据ETDRS网格的定义，冠心病组外上（out-S）区视网膜内外层均明显变薄。冠心病组总体二维分形维数（FD）显著低于冠心病组(1.72±0.03 vs. 1.73±0.02,P <；0.001)和血管骨架密度（VSD）(26.61±4.52∶28.50±3.40,P <；0.001)，与对照组相比。三维血管密度（VD）特征组间差异有统计学意义（19.23±5.67 vs. 20.69±5.15,P = 0.048）。结论视网膜厚度变薄和血管密度降低与冠心病相关，可作为评估冠状动脉疾病的有价值、有成本效益的生物标志物。
{"title":"Novel 2D/3D vascular biomarkers reveal association between fundus changes and coronary heart disease","authors":"Xiaoyu Dong , Yu Zou , Xiaohui Li , Na Su , Yuchen Wen , Jiale Fang , Xianqi Li , Qiang Chen , Junhong Wang","doi":"10.1016/j.mvr.2025.104793","DOIUrl":"10.1016/j.mvr.2025.104793","url":null,"abstract":"<div><h3>Purpose</h3><div>To compare structural and vascular differences in the macular region of the retina using optical coherence tomography (OCT)/OCT angiography (OCTA) between coronary angiography (CAG)-confirmed coronary heart disease (CHD) patients and non-CHD individuals.</div></div><div><h3>Methods</h3><div>The study included 340 eyes from 180 CHD patients and 136 eyes from 68 controls. Imaging was conducted using the AngioVue OCT device with a macula-centered 6 mm ∗ 6 mm field of view. Retinal thickness and 2D/3D vascular-related biomarkers were derived using existing retinal layer segmentation software, and our previously proposed 2D/3D vascular and 3D foveal avascular zone segmentation methods. Statistical analyses included <em>t</em>-tests, Mann-Whitney <em>U</em> tests, chi-square tests, and Pearson's correlation.</div></div><div><h3>Results</h3><div>The CHD group exhibited significantly lower retinal nerve fiber layer (RNFL) thickness (r = −0.20, P < 0.001) in the inner inferior (I) region, based on macular region layer segmentation. For the 3D OCT images, as defined by the ETDRS grid, both the inner and outer retina layers in the outer superior (out-S) region were significantly thinner in the CHD group. The CHD group showed significantly lower overall 2D fractal dimension (FD) (1.72 ± 0.03 vs. 1.73 ± 0.02, P < 0.001) and vessel skeleton density (VSD) (26.61 ± 4.52 vs. 28.50 ± 3.40, P < 0.001) compared to the control group. The proposed 3D vascular density (VD) feature showed a significant difference between the groups (19.23 ± 5.67 vs. 20.69 ± 5.15, P = 0.048).</div></div><div><h3>Conclusion</h3><div>Thinning of retinal thickness and reduced vascular density are associated with CHD and may serve as valuable, cost-effective biomarkers for assessing coronary artery disease assessment.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"159 ","pages":"Article 104793"},"PeriodicalIF":2.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395469","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 : 2025-02-07DOI: 10.1016/j.mvr.2025.104794
Lianfu Zhang , Shihui Ni , Weiwen Zhang , Jian Shi , Jun Ding , Xudong Xu , Shengbang Zhang , Yongming Zhang , Tao Jiang
Endothelial progenitor cells (EPCs), which are precursors for endothelial cells, possess the capability of repairing vascular damage and predicting the extent of early vascular injury. However, the role of EPCs in the repair of fusiform aneurysms is not clear. Here, we constructed a fusiform aneurysm model using pancreatic elastase digestion and validated the improvement effect of EPCs through histological staining and immunofluorescence. HE staining and elastic fiber staining showed destruction of the tunica adventitia in the fusiform aneurysm, marked dilatation of the arterial lumen, and thinning of the elastic lamina in the fusiform aneurysm. In the fusiform aneurysm group, the concentration of vascular endothelial growth factor (VEGF) was notably decreased compared to both the control and the saline group. The level of EPCs in the peripheral blood was decreased in the model group. Transplantation of EPCs into fusiform aneurysms promoted vascular repair, indicated by the decrease of myeloperoxidase (MPO), advanced oxidation protein products (AOPP), matrix metalloproteinase-9 (MMP-9), platelet factor 4 (PF4), and Fe2+. The level of VEGF was also elevated after EPCs transplantation. Finally, we noted a marked rise in lactate level in the peripheral blood of fusiform aneurysms. Lactate treatment led to an elevation of H3K18la levels in EPCs and inhibited cell proliferation. In conclusion, this study discovered that in mice with fusiform aneurysms, elevated lactate levels in the peripheral blood trigger histone lactylation, such impeding the proliferation of EPCs. Transplantation of EPCs into fusiform aneurysms facilitated aneurysm repair. These findings lay the groundwork for EPCs in the treatment of fusiform aneurysms.
{"title":"Transplantation of autologous endothelial progenitor cells promotes the repair of fusiform aneurysms","authors":"Lianfu Zhang , Shihui Ni , Weiwen Zhang , Jian Shi , Jun Ding , Xudong Xu , Shengbang Zhang , Yongming Zhang , Tao Jiang","doi":"10.1016/j.mvr.2025.104794","DOIUrl":"10.1016/j.mvr.2025.104794","url":null,"abstract":"<div><div>Endothelial progenitor cells (EPCs), which are precursors for endothelial cells, possess the capability of repairing vascular damage and predicting the extent of early vascular injury. However, the role of EPCs in the repair of fusiform aneurysms is not clear. Here, we constructed a fusiform aneurysm model using pancreatic elastase digestion and validated the improvement effect of EPCs through histological staining and immunofluorescence. HE staining and elastic fiber staining showed destruction of the tunica adventitia in the fusiform aneurysm, marked dilatation of the arterial lumen, and thinning of the elastic lamina in the fusiform aneurysm. In the fusiform aneurysm group, the concentration of vascular endothelial growth factor (VEGF) was notably decreased compared to both the control and the saline group. The level of EPCs in the peripheral blood was decreased in the model group. Transplantation of EPCs into fusiform aneurysms promoted vascular repair, indicated by the decrease of myeloperoxidase (MPO), advanced oxidation protein products (AOPP), matrix metalloproteinase-9 (MMP-9), platelet factor 4 (PF4), and Fe<sup>2+</sup>. The level of VEGF was also elevated after EPCs transplantation. Finally, we noted a marked rise in lactate level in the peripheral blood of fusiform aneurysms. Lactate treatment led to an elevation of H3K18la levels in EPCs and inhibited cell proliferation. In conclusion, this study discovered that in mice with fusiform aneurysms, elevated lactate levels in the peripheral blood trigger histone lactylation, such impeding the proliferation of EPCs. Transplantation of EPCs into fusiform aneurysms facilitated aneurysm repair. These findings lay the groundwork for EPCs in the treatment of fusiform aneurysms.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"159 ","pages":"Article 104794"},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382872","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 : 2025-02-06DOI: 10.1016/j.mvr.2025.104792
Zhengxin Tang , Anthony E. Felder , Mahnaz Shahidi
Blood flow regulation has been shown to be compromised in common ocular diseases, such as diabetic retinopathy and glaucoma. The capacity of the retinal vessels to regulate blood flow can potentially serve as an oculomics biomarker for evaluating ocular and systemic diseases. Pulse-propagated intravascular pressure waves cause deformations of the vessel walls, thus offering a means to interrogate vascular compliance. The purpose of the current study is to report a method for measuring retinal pulse-propagated wave velocity (rPWV) based on spectral analysis of pulsatile intensity waveforms in human circumpapillary retinal vasculature. Arterial and venous rPWV values, as well as inter-subject variabilities of rPWV in non-diabetic and diabetic subjects, are reported. Preliminary results demonstrated the feasibility of this method for measuring rPWV and its potential for assessment of vascular plasticity in response to blood flow changes due to ocular and systemic diseases.
{"title":"Feasibility of a method for measurement of retinal pulse-propagated wave velocity in humans","authors":"Zhengxin Tang , Anthony E. Felder , Mahnaz Shahidi","doi":"10.1016/j.mvr.2025.104792","DOIUrl":"10.1016/j.mvr.2025.104792","url":null,"abstract":"<div><div>Blood flow regulation has been shown to be compromised in common ocular diseases, such as diabetic retinopathy and glaucoma. The capacity of the retinal vessels to regulate blood flow can potentially serve as an oculomics biomarker for evaluating ocular and systemic diseases. Pulse-propagated intravascular pressure waves cause deformations of the vessel walls, thus offering a means to interrogate vascular compliance. The purpose of the current study is to report a method for measuring retinal pulse-propagated wave velocity (rPWV) based on spectral analysis of pulsatile intensity waveforms in human circumpapillary retinal vasculature. Arterial and venous rPWV values, as well as inter-subject variabilities of rPWV in non-diabetic and diabetic subjects, are reported. Preliminary results demonstrated the feasibility of this method for measuring rPWV and its potential for assessment of vascular plasticity in response to blood flow changes due to ocular and systemic diseases.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"159 ","pages":"Article 104792"},"PeriodicalIF":2.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350060","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 : 2025-01-28DOI: 10.1016/j.mvr.2025.104791
Rebecca Patrick , Briana D. Pando , Clement Yang, Alexandra Aponte, Fang Wang, Tom Ewing, Yonggang Ma, Sarah Y. Yuan, Mack H. Wu
Intestinal ischemia-reperfusion (I/R) injury occurs under various surgical or disease conditions, where tissue hypoxia followed by reoxygenation results in the production of oxygen radicals and inflammatory mediators. These substances can target the endothelial barrier, leading to microvascular leakage. In this study, we induced intestinal I/R injury in mice by occluding the superior mesenteric artery, followed by removing the clamp to resume blood circulation. We assessed microvascular permeability to plasma proteins in vivo using intravital microscopy, measuring the time-dependent tracer distribution in the intravascular versus extravascular space in the mouse mesentery. Additionally, we examined endothelial cell-cell adhesive barrier resistance and junction morphology in cultured endothelial cell monolayers. At the molecular level, FAK inhibition similarly inhibited endothelial junction opening and barrier dysfunction in response to hydrogen peroxide-induced oxidative stress. To further investigate FAK's role with tissue/cell specificity, we developed an endothelial-specific inducible FAK knockout mouse model by crossbreeding FAK-floxed (FAKfl/fl) mice with Tie-2-CreERT2 transgenic mice. Compared to their wild-type controls, endothelial-specific FAK-deficient mice showed a blunted microvascular hyperpermeability response following I/R injury in the gut. Overall, our study demonstrates that FAK plays a significant signaling role in mediating endothelial barrier dysfunction and microvascular leakage during ischemia-reperfusion injury.
{"title":"Focal adhesion kinase mediates microvascular leakage and endothelial barrier dysfunction in ischemia-reperfusion injury","authors":"Rebecca Patrick , Briana D. Pando , Clement Yang, Alexandra Aponte, Fang Wang, Tom Ewing, Yonggang Ma, Sarah Y. Yuan, Mack H. Wu","doi":"10.1016/j.mvr.2025.104791","DOIUrl":"10.1016/j.mvr.2025.104791","url":null,"abstract":"<div><div>Intestinal ischemia-reperfusion (I/R) injury occurs under various surgical or disease conditions, where tissue hypoxia followed by reoxygenation results in the production of oxygen radicals and inflammatory mediators. These substances can target the endothelial barrier, leading to microvascular leakage. In this study, we induced intestinal I/R injury in mice by occluding the superior mesenteric artery, followed by removing the clamp to resume blood circulation. We assessed microvascular permeability to plasma proteins in vivo using intravital microscopy, measuring the time-dependent tracer distribution in the intravascular versus extravascular space in the mouse mesentery. Additionally, we examined endothelial cell-cell adhesive barrier resistance and junction morphology in cultured endothelial cell monolayers. At the molecular level, FAK inhibition similarly inhibited endothelial junction opening and barrier dysfunction in response to hydrogen peroxide-induced oxidative stress. To further investigate FAK's role with tissue/cell specificity, we developed an endothelial-specific inducible FAK knockout mouse model by crossbreeding FAK-floxed (FAK<sup>fl/fl</sup>) mice with Tie-2-CreER<sup>T2</sup> transgenic mice. Compared to their wild-type controls, endothelial-specific FAK-deficient mice showed a blunted microvascular hyperpermeability response following I/R injury in the gut. Overall, our study demonstrates that FAK plays a significant signaling role in mediating endothelial barrier dysfunction and microvascular leakage during ischemia-reperfusion injury.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"159 ","pages":"Article 104791"},"PeriodicalIF":2.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066809","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 : 2025-01-19DOI: 10.1016/j.mvr.2025.104783
Freya Richter , Moa Nilsson , Joakim Henricson , Carl Johan Östgren , Marcus Larsson , Tomas Strömberg , Ingemar Fredriksson , Fredrik Iredahl
Introduction
Little is known about the day-to-day variability of different skin microcirculation parameters, and how this variability is influenced by age and sex. The aim was to examine the day-to-day variability of microcirculatory parameters in relation to age and sex.
Methods
The cutaneous microcirculation was measured using a fiber optic probe integrating laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) to measure oxygen saturation, red blood cell (RBC) tissue fraction, speed-resolved and conventional perfusion. Measurements at two separate days were compared during baseline, a 5-min occlusion and during the following post-occlusive reactive hyperemia (PORH) period on the volar forearm and dorsal foot in totally 48 men and women aged 20–30 and 50–60 years, respectively. Variability was expressed as the coefficient of variation CV and repeatability as the intraclass correlation coefficient ICC.
Results
Peak oxygen saturation during PORH had the lowest day-to-day variability for the forearm (CV = 2.1 %) and the foot (CV = 3.8 %) as well as an excellent repeatability (ICC = 0.80 and ICC = 0.82, respectively). Older women had a higher day-to-day variability in baseline conventional perfusion compared to younger women on the forearm (p = 0.007). On the foot, older women had a lower day-to-day variability than younger women for baseline oxygen saturation (p = 0.006) and peak RBC tissue concentration (p = 0.008). Older men had a lower day-to-day variability than younger men for baseline oxygen saturation (p = 0.012) but a higher variability for baseline and peak RBC tissue concentration (p = 0.008 and p = 0.002) on the foot.
Conclusion
Peak oxygen saturation had the lowest day-to-day variability of the measured parameters. A lower value of peak oxygen saturation has previously been associated with increasing systematic coronary risk implying that this is a suitable parameter for measuring microcirculatory dysfunction. Sex and age only affected the day-to-day variability of very few parameters.
{"title":"Sex and age-related day-to-day variability in the skin microcirculation during post-occlusive reactive hyperemia","authors":"Freya Richter , Moa Nilsson , Joakim Henricson , Carl Johan Östgren , Marcus Larsson , Tomas Strömberg , Ingemar Fredriksson , Fredrik Iredahl","doi":"10.1016/j.mvr.2025.104783","DOIUrl":"10.1016/j.mvr.2025.104783","url":null,"abstract":"<div><h3>Introduction</h3><div>Little is known about the day-to-day variability of different skin microcirculation parameters, and how this variability is influenced by age and sex. The aim was to examine the day-to-day variability of microcirculatory parameters in relation to age and sex.</div></div><div><h3>Methods</h3><div>The cutaneous microcirculation was measured using a fiber optic probe integrating laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) to measure oxygen saturation, red blood cell (RBC) tissue fraction, speed-resolved and conventional perfusion. Measurements at two separate days were compared during baseline, a 5-min occlusion and during the following post-occlusive reactive hyperemia (PORH) period on the volar forearm and dorsal foot in totally 48 men and women aged 20–30 and 50–60 years, respectively. Variability was expressed as the coefficient of variation CV and repeatability as the intraclass correlation coefficient ICC.</div></div><div><h3>Results</h3><div>Peak oxygen saturation during PORH had the lowest day-to-day variability for the forearm (CV = 2.1 %) and the foot (CV = 3.8 %) as well as an excellent repeatability (ICC = 0.80 and ICC = 0.82, respectively). Older women had a higher day-to-day variability in baseline conventional perfusion compared to younger women on the forearm (<em>p</em> = 0.007). On the foot, older women had a lower day-to-day variability than younger women for baseline oxygen saturation (<em>p</em> = 0.006) and peak RBC tissue concentration (<em>p</em> = 0.008). Older men had a lower day-to-day variability than younger men for baseline oxygen saturation (<em>p</em> = 0.012) but a higher variability for baseline and peak RBC tissue concentration (p = 0.008 and <em>p</em> = 0.002) on the foot.</div></div><div><h3>Conclusion</h3><div>Peak oxygen saturation had the lowest day-to-day variability of the measured parameters. A lower value of peak oxygen saturation has previously been associated with increasing systematic coronary risk implying that this is a suitable parameter for measuring microcirculatory dysfunction. Sex and age only affected the day-to-day variability of very few parameters.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"159 ","pages":"Article 104783"},"PeriodicalIF":2.9,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008276","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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