Microvascular researchPub Date : 2025-09-01Epub Date: 2025-07-07DOI: 10.1016/j.mvr.2025.104841
Arnaldo Dubin
{"title":"Letter to the editor: “Pitfalls in the assessment of microcirculation”","authors":"Arnaldo Dubin","doi":"10.1016/j.mvr.2025.104841","DOIUrl":"10.1016/j.mvr.2025.104841","url":null,"abstract":"","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104841"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144572148","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}
{"title":"Quantitative image analysis of nailfold capillaries during an in-hospital education program for type 2 diabetes or obesity","authors":"Kengo Miyoshi , Masatomo Chikamori , Takashi Ando , Kengo Nakata , Tomohisa Aoyama , Yukiko T. Matsunaga , Toshimasa Yamauchi","doi":"10.1016/j.mvr.2025.104830","DOIUrl":"10.1016/j.mvr.2025.104830","url":null,"abstract":"<div><div>Nailfold capillaries are small U-shaped vessels located beneath the skin at the proximal part of the fingernail, and their morphology changes owing to various diseases. This study quantitatively analyzed nailfold capillaries using microscopy in patients hospitalized for 2 weeks for education and treatment of type 2 diabetes (T2D) or obesity. Our results suggest that nailfold arterial diameter and smoking history are useful predictors of diabetic neuropathy. An elevated urinary albumin-to-creatinine ratio correlated with decreased venous diameter during hospitalization, reflecting latent intravascular hypoalbuminemia in patients with diabetic nephropathy. Both body mass index and short-term weight reduction during hospitalization correlated with the color contrast between the capillaries and the perivascular zone, defined as delta E. These results suggest that the morphology of nailfold capillaries in T2D and obesity could be useful indicators of diabetic neuropathy and nephropathy, with delta E being a useful indicator of extracellular water volume in these populations. This is the first study to observe short-term changes in nailfold capillary morphology in relation to interventions for lifestyle-related diseases.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104830"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255406","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}
Microvascular researchPub Date : 2025-09-01Epub Date: 2025-07-13DOI: 10.1016/j.mvr.2025.104843
Xin Yu , Zhen Yang , Zhilan Ma , Ru Yan , Jianzhong Zhang
{"title":"The electrophysiological effects of angiotensin 1–7 on hypertrophic myocardium in spontaneously hypertensive rats","authors":"Xin Yu , Zhen Yang , Zhilan Ma , Ru Yan , Jianzhong Zhang","doi":"10.1016/j.mvr.2025.104843","DOIUrl":"10.1016/j.mvr.2025.104843","url":null,"abstract":"<div><div>This study aimed to explore the effects of Angiotensin 1–7 (Ang1–7) on electrophysiological remodeling of hypertensive hypertrophic myocardium in spontaneously hypertensive rats (SHR). Thirty male SHR rats were equally divided into three groups: SHR control group (SHR<img>C) treated with saline; Ang1–7 group (SHR-A) treated with Ang1–7[25 μg·(kg min)<sup>−1</sup>] and Ang1–7 blocker group (SHR<img>B) treated with A779 [72 μg·(kg min)<sup>−1</sup>]. Wistar-Kyoto (WKY) rats (<em>n</em> = 10) were used as a normotensive group. The treatment period was 5 weeks. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Echocardiography was used to evaluate cardiac function. The ventricular myocytes were isolated for evaluation of electrophysiological remodeling of myocardium using microelectrode and patch clamp techniques. When compared with those in WKY rats before treatment, systolic and diastolic pressures were significantly higher in SHR (<em>P</em> < 0.01 and <em>P</em> < 0.001 respectively), left ventricular end-diastolic diameter (LVEDd) was significantly lower (<em>P</em> < 0.05), while diastolic interventricular septum thickness (IVSd), diastolic left ventricular posterior wall thickness (LVPWd) were significantly greater in SHR (<em>P</em> < 0.01). After 5 weeks of treatment, compared with SHR-C group, SBP, DBP, IVSd, LVPWd in SHR-A group were lower significantly (<em>P</em> < 0.05), while SBP in SHR-B group was significantly higher (<em>P</em> < 0.05). Compared with WKY group, the resting potential (RP), action potential amplitude (APA) and transient sodium current (<em>I</em><sub>Na-T</sub>) in SHR group were significantly lower (<em>P</em> < 0.05), and the action potential duration (APD<sub>20</sub>, APD<sub>50</sub> and APD<sub>90</sub>) in SHR group was greater (<em>P</em> < 0.05). After Ang1–7 intervention, RP, APA and <em>I</em><sub>Na-T</sub> were significantly greater in SHR-A than those in SHR-C (<em>P</em> < 0.05), and APD in SHR-A significantly lower than that in SHR-C (<em>P</em> < 0.05). Taken together, these results demonstrated that Ang1–7 can not only decrease the blood pressure, but reverse the myocardial hypertrophy and electrophysiological remodeling as well in SHR rats.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104843"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642932","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}
Microvascular researchPub Date : 2025-09-01Epub Date: 2025-06-26DOI: 10.1016/j.mvr.2025.104838
Ruijin Hong , Beilei Li , Hui Chen , Jiaxin Zhong , Yuxiang Chen , Yuanming Yan , Lianglong Chen , Qin Chen , Yukun Luo
{"title":"Predictive value of the average three-vessel microvascular resistance in patients with non-ST-segment elevation myocardial infarction after percutaneous coronary intervention","authors":"Ruijin Hong , Beilei Li , Hui Chen , Jiaxin Zhong , Yuxiang Chen , Yuanming Yan , Lianglong Chen , Qin Chen , Yukun Luo","doi":"10.1016/j.mvr.2025.104838","DOIUrl":"10.1016/j.mvr.2025.104838","url":null,"abstract":"<div><h3>Objectives</h3><div>We investigated the predictive value of the average microvascular resistance of the three main vessels (3VA-AMR) for the prognosis of patients with non-ST-segment elevation myocardial infarction (NSTEMI) after percutaneous coronary intervention (PCI).</div></div><div><h3>Methods</h3><div>This study was conducted on patients with NSTEMI who underwent PCI between March 1, 2021, and February 28, 2022, at Fujian Medical University Union Hospital. Quantitative flow ratio (QFR) analysis was conducted on all patients' PCI angiography images to assess postoperative QFR and angio-based microvascular resistance (AMR) for three main vessels. All enrolled patients were devided into two groups based on the criteria for coronary microvascular dysfunction (CMD): high 3VA-AMR group and low 3VA-AMR group. The primary outcome was 2-year major adverse cardiac events (MACEs), including cardiovascular death, myocardial infarction, and ischemia-driven revascularization.</div></div><div><h3>Results</h3><div>A total of 290 patients were included in the final analysis. Compared with the low 3VA-AMR group, the three vessels of high 3VA-AMR group showed lower area stenosis (49.46 ± 13.70 % vs. 52.93 ± 15.43 %,<em>P</em> = 0.001), higher QFR value (0.92 ± 0.05 vs. 0.88 ± 0.09, P < 0.001), and higher AMR value (274.50 [257.33–301.42] mmHg*s/m vs. 208.00 [182.00–231.83] mmHg*s/m, P < 0.001). The incidence of 2-year MACEs was significantly higher in the high 3VA-AMR group than in the low 3VA-AMR group (21.90 % vs. 10.27 %, <em>P</em> = 0.007). Univariate and multivariate Cox regression analyses confirmed that 3VA-AMR was independently associated with 2-year MACEs (HR:1.007, 95 % CI:1.004–1.010, <em>P</em> < 0.001). The Kaplan–Meier method further confirmed the difference in 2-year MACE risk between two groups. Receiver operating characteristic curve analysis showed a significant correlation between 3VA-AMR and MACE (area under the curve: 0.701, <em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>3VA-AMR was an independent risk factor for 2-year MACEs in NSTEMI patients. Compared with target-vessel AMR, 3VA-AMR demonstrated superior predictive value for 2-year MACEs following PCI.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104838"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528670","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}
Microvascular researchPub Date : 2025-09-01Epub Date: 2025-06-27DOI: 10.1016/j.mvr.2025.104834
Mayinuer Yusufu , Robert N. Weinreb , Mengtian Kang , Algis J. Vingrys , Xianwen Shang , Lei Zhang , Danli Shi , Mingguang He
{"title":"Structural and causal links between retinal vascular geometry and neural layer thickness","authors":"Mayinuer Yusufu , Robert N. Weinreb , Mengtian Kang , Algis J. Vingrys , Xianwen Shang , Lei Zhang , Danli Shi , Mingguang He","doi":"10.1016/j.mvr.2025.104834","DOIUrl":"10.1016/j.mvr.2025.104834","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate structural relationships between retinal vasculometry from color fundus photography (CFP) and neural layers obtained from Optical Coherence Tomography (OCT) scans.</div></div><div><h3>Methods</h3><div>This cross-sectional study used the Retina-based Microvascular Health Assessment System (RMHAS) to extract retinal vascular measurements in the 6*6 mm area centered on the macular region and analyzed their associations with OCT parameters. We investigated both pairwise correlations between individual retinal layers and vascular parameters and associations between sets of variables. Mendelian randomization was employed to investigate potential causality.</div></div><div><h3>Results</h3><div>Data from 67,918 eyes of 43,029 participants were included. Among neural layers, Ganglion Cell-Inner Plexiform Layer (GC-IPL) showed the most notable correlations with vascular Density and Complexity (<em>r</em> = 0.199 for arterial Vessel Area Density and <em>r</em> = 0.175 for Number of Segments). Inner Nuclear Layer (INL) thickness correlated with Width (<em>r</em> = 0.122) and arterial Vessel Area Density (<em>r</em> = 0.127). Mendelian randomization indicated a bidirectional causal relationship. Genetically predicted higher Vessel Density was associated with increased thickness across various retinal layers, with standardized effect size of 1.50 on Inner Segment/Outer Segment + Photoreceptor Segment thickness. Genetically predicted increases in retinal layer thicknesses, particularly the Outer Plexiform Layer, were linked to higher Vessel Density (standardized effect size 0.45) and Fractal Dimension (standardized effect size 0.48).</div></div><div><h3>Conclusions</h3><div>GC-IPL and INL were positively associated with vascular Density and Caliber. Multidimensional relationships indicate a complementary nature between retinal vascular and neural parameters, highlighting their value as a composite biomarker. Mendelian Randomization uncovered a bidirectional causal relationship, providing insights into novel therapeutic approaches targeting vascular and neuronal components.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104834"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144522807","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}
Microvascular researchPub Date : 2025-09-01Epub Date: 2025-06-24DOI: 10.1016/j.mvr.2025.104833
Yang He , Jian Lin , Yi Li , Xiaobo Cheng , Tong Wang , Wei Wang , Weixing Zeng , Yongsheng Li
{"title":"DDIT4 knockdown suppresses venous malformation progression by inhibiting NF-κB signaling as a potential therapeutic target","authors":"Yang He , Jian Lin , Yi Li , Xiaobo Cheng , Tong Wang , Wei Wang , Weixing Zeng , Yongsheng Li","doi":"10.1016/j.mvr.2025.104833","DOIUrl":"10.1016/j.mvr.2025.104833","url":null,"abstract":"<div><h3>Background</h3><div>This study aims to investigate the regulatory role and underlying molecular mechanisms of DNA Damage Inducible Transcript 4 (DDIT4) in the pathogenesis of Venous Malformations (VMs), providing foundational experimental evidence for potential targeted therapies.</div></div><div><h3>Methods</h3><div>Bioinformatic analysis identified <em>DDIT4</em> as a key differentially expressed gene in VMs, and the sgGSEA method was employed to predict its potential biological functions. Immunohistochemical staining and immunofluorescence were performed to validate the expression level of DDIT4 and its association with vascular density. A lentiviral VMs cell model was established to assess DDIT4 expression levels. The effects of DDIT4 knockdown on VMs cell function were evaluated, with mechanistic insights gained through transcriptome sequencing and Western blot analysis. Further validation was performed using 3D VMs cell models and nude mouse xenografts with DDIT4 knockdown. Additionally, exogenous functional rescue experiments were conducted by activating the NF-κB pathway with lipopolysaccharide (LPS) in DDIT4 knockdown VMs 3D cell models and nude mouse xenografts to further investigate the role of DDIT4.</div></div><div><h3>Results</h3><div>DDIT4 was upregulated in VMs tissues and correlated with angiogenesis. DDIT4 knockdown increased cell roundness, inhibited proliferation, migration, and NF-κB pathway activation, and blocked angiogenesis in VMs 3D models and lesion formation in nude mouse xenografts, while suppressing the NF-κB pathway in both. NF-κB pathway activation restored angiogenesis in both models.</div></div><div><h3>Conclusions</h3><div>DDIT4 knockdown inhibits VMs progression by suppressing the NF-κB pathway, suggesting that DDIT4 may serve as a potential therapeutic target.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104833"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144506523","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}
{"title":"Acute effects of belt electrode-skeletal muscle electrical stimulation on microvascular responsiveness of the gastrocnemius muscle in healthy young men","authors":"Hajime Tamiya , Hina Kawashiri , Toshiaki Miyamoto , Yuko Kurosawa , Takafumi Hamaoka , Atsuhiro Tsubaki","doi":"10.1016/j.mvr.2025.104840","DOIUrl":"10.1016/j.mvr.2025.104840","url":null,"abstract":"<div><h3>Purpose</h3><div>Belt electrode-skeletal muscle electrical stimulation (B-SES) improves muscle strength, mass, and exercise tolerance. However, its effects on skeletal muscle microvascular responsiveness remain unclear. In this study, we investigated the acute effects of a single B-SES session on gastrocnemius microvascular responsiveness in healthy young men.</div></div><div><h3>Methods</h3><div>In this randomized crossover study, 12 healthy young men (mean age: 20.8 ± 1.0 years) underwent two 20-min conditions: electrical stimulation at the sensory threshold (Sham, <em>n</em> = 12) and at the maximum intensity not causing discomfort (B-SES, n = 12). Gastrocnemius metabolic rate (tissue oxygen saturation [StO<sub>2</sub>] downslope) and microvascular reperfusion rate (StO<sub>2</sub> upslope) were assessed using near-infrared spectroscopy and a vascular occlusion test.</div></div><div><h3>Results</h3><div>In the B-SES condition, the StO<sub>2</sub> downslope significantly steepened (Pre: −0.15 ± 0.03 %·s<sup>−1</sup>, Post: −0.20 ± 0.03 %·s<sup>−1</sup>, <em>p</em> = 0.002). The StO<sub>2</sub> upslope also significantly steepened (Pre: 1.58 ± 0.52 %·s<sup>−1</sup>, Post: 2.56 ± 0.71 %·s<sup>−1</sup>, <em>p</em> < 0.001). A significant negative correlation was observed between the StO<sub>2</sub> downslope and StO<sub>2</sub> upslope (<em>r</em> = −0.581, <em>p</em> = 0.047). No significant changes were observed in the Sham condition.</div></div><div><h3>Conclusions</h3><div>A single B-SES session applied to the lower extremity significantly increased gastrocnemius metabolic rate and was associated with enhanced microvascular reperfusion. These findings suggest B-SES may be a useful therapeutic approach to improving microvascular responsiveness, particularly in individuals with limited exercise capacity.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104840"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595548","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}
Microvascular researchPub Date : 2025-09-01Epub Date: 2025-07-02DOI: 10.1016/j.mvr.2025.104835
Simone Woodruff , Benjamin Zimmerman , Kevin J. Elk , Jennifer E. Jenks , Danica Bojovic , Anusha Mishra
{"title":"Kinetics of thromboxane A2 receptor-driven vascular tone in the cerebral cortex ex vivo","authors":"Simone Woodruff , Benjamin Zimmerman , Kevin J. Elk , Jennifer E. Jenks , Danica Bojovic , Anusha Mishra","doi":"10.1016/j.mvr.2025.104835","DOIUrl":"10.1016/j.mvr.2025.104835","url":null,"abstract":"<div><div><em>Ex vivo</em> imaging in acute cortical brain slices is a valuable tool to assess neurovascular coupling and is particularly useful for studying active, local changes in microvascular compartments in isolation from upstream or downstream changes in flow. However, the lack of vascular perfusion pressure <em>ex vivo</em> results in loss of vascular tone, which must be restored prior to experiments to unmask dilatory signals. The thromboxane A2 receptor agonist U46619 is a widely used preconstrictor, yet its dose-response properties and kinetics of action on different vascular segments are not fully known. Here, we characterize the effects of U46619 on cortical arterioles and capillaries in <em>ex vivo</em> slices from rats and mice. Dose response curves tested in acute rat brain slices using 0 to 1000 nM U46619 showed that maximal constriction is reached at ∼300 nM in both arterioles and capillaries. Extended application of 200 nM U46619 (∼66 % maximal dose) over 2 h revealed that, on average, capillaries constrict faster than arterioles in rat brain slices. Cross-species examination in mouse tissue showed that vessels in mouse brain slices respond faster and constrict stronger on average than in rat brain slices, and that mouse capillaries also constrict faster than mouse arterioles. Our observations suggest that near-maximal preconstriction can be achieved in <em>ex vivo</em> experiments using 200–300 nM U46619, with a minimum incubation time of 20 min for studies involving capillaries and at least 30 min for studies involving arterioles.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104835"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144556874","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}
Microvascular researchPub Date : 2025-09-01Epub Date: 2025-07-02DOI: 10.1016/j.mvr.2025.104839
Minyoung Kwak , Brian Benitez , Clara J. Mitchinson , Erik R. Snell , Haley C. Bergstrom
{"title":"Influence of isometric RPE-clamp exercise on fatigability, muscle oxygenation dynamics, and microvascular function in healthy young adults","authors":"Minyoung Kwak , Brian Benitez , Clara J. Mitchinson , Erik R. Snell , Haley C. Bergstrom","doi":"10.1016/j.mvr.2025.104839","DOIUrl":"10.1016/j.mvr.2025.104839","url":null,"abstract":"<div><h3>Purpose</h3><div>This study investigated fatigability, reflected by torque responses and time to task failure (TTF), and time course of muscle oxygenation (SmO<sub>2</sub>) dynamics, as well as microvascular function assessed by near-infrared spectroscopy-vascular occlusion test (NIRS-VOT), in response to low-intensity, isometric forearm flexion anchored to a constant rating of perceived exertion (RPE) level of 3 (0–10 scale).</div></div><div><h3>Methods</h3><div>Twenty-five healthy young adults (22.9 ± 4.8 yr) completed a pre-exercise VOT, maximal voluntary isometric contraction (MVIC), and RPE-clamp exercise (RPE = 3), followed by post-exercise MVIC and VOT. Initial torque, TTF, and SmO<sub>2</sub> dynamics were recorded during the RPE-clamp exercise. The time course of SmO<sub>2</sub> was analyzed in 5 % TTF segments. During the VOTs, slope 1 (desaturation rate), minimum SmO<sub>2</sub>, slope 2 (reperfusion rate), maximum SmO<sub>2</sub>, and area under the curve (AUC) were recorded.</div></div><div><h3>Results</h3><div>MVIC torque significantly decreased from pre- to post-exercise (−13.9 % ± 14.0 %; <em>p</em> < 0.001). Initial torque was 23.3 ± 10.3 % MVIC, and TTF was 436.3 ± 252.0 s. SmO<sub>2</sub> declined significantly from 0 % to 5 % TTF (<em>p</em> = 0.005), but returned to the initial value and remained stable across subsequent time intervals. Compared to pre-VOT, post-VOT exhibited significantly lower slope 1 (<em>p</em> < 0.001) and minimum SmO<sub>2</sub> (<em>p</em> = 0.002), and greater maximum SmO<sub>2</sub> (<em>p</em> = 0.013), while slope 2 (<em>p</em> = 0.065) and AUC (<em>p</em> = 0.379) were unchanged.</div></div><div><h3>Conclusions</h3><div>During the RPE-clamp exercise, the voluntary reduction in torque to maintain the assigned RPE likely resulted in stable muscle oxygen availability, preventing the development of hypoxic stimulus needed to enhance microvascular responsiveness. However, the low-intensity isometric RPE-clamp exercise combined with a post-VOT may enhance muscle aerobic metabolism through sustained oxygen utilization.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104839"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548508","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}
Microvascular researchPub Date : 2025-09-01Epub Date: 2025-06-25DOI: 10.1016/j.mvr.2025.104837
Hyerim Park , Steven L. Medarev , Joshua J. Maraj , Alexis Restrepo , Steven W. Copp , Judy M. Muller-Delp
{"title":"Nrf2 deficiency blunts exercise training-induced adaptations of coronary resistance arteries","authors":"Hyerim Park , Steven L. Medarev , Joshua J. Maraj , Alexis Restrepo , Steven W. Copp , Judy M. Muller-Delp","doi":"10.1016/j.mvr.2025.104837","DOIUrl":"10.1016/j.mvr.2025.104837","url":null,"abstract":"<div><div>Exercise training upregulates nuclear factor erythroid 2-related factor 2 (Nrf2) expression and antioxidant production in various tissues; however, little is known about the role of Nrf2 in exercise training-induced adaptations of blood vessels. This study investigated how deletion of Nrf2 affects vasomotor function in coronary resistance arteries in sedentary and exercise-trained rats. Wild-type (WT) and Nrf2 knockout (KO) rats underwent 10 weeks of treadmill exercise or remained sedentary. Coronary resistance arteries were isolated for assessment of vasomotor responses. In resistance arteries from Nrf2 KO rats, endothelin-induced constriction was blunted, but exercise training partially restored responsiveness to endothelin; after exercise training, responses to endothelin were not different between arteries from WT and Nrf2 KO rats. Similarly, KCl-induced constriction was reduced in arteries from Nrf2 KO rats, but exercise training reversed this loss of responsiveness to KCl. Nitric oxide (NO)-mediated vasodilation of coronary resistance arteries was not altered by deletion of Nrf2; however, exercise training enhanced NO-mediated dilation in arteries from WT, but not Nrf2 KO rats. Similarly, exercise training increased vasodilation to low concentrations of potassium (10 and 20 mM KCl) in arteries from WT, but not Nrf2 KO rats. These findings suggest that Nrf2 is critical to maintenance of contractile responses in coronary resistance arteries, but exercise training can restore contractile function through Nrf2-independent mechanisms. In contrast, vasodilatory responses to NO and low-level potassium are maintained in coronary resistance arteries from Nrf2-deficient rats, but exercise training fails to enhance these vasodilatory responses in the absence of Nrf2.</div></div>","PeriodicalId":18534,"journal":{"name":"Microvascular research","volume":"161 ","pages":"Article 104837"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512168","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}