Coronary microvascular dysfunction (CMD) drives angina in patients with ischemia with non-obstructive coronary artery disease, a condition that is more prevalent in females. Effective treatment strategies remain limited, in part, due to the scarcity of physiologically relevant animal models. Indeed, while CMD has been studied in animals with diabetes or fed high-fat diets, hypertension is the predominant risk factor for CMD in humans, but is not captured by these models.
Methods
We characterized the CMD that arose in female spontaneously hypertensive rats (SHRs). We measured coronary flow reserve, alongside basic cardiovascular function in SHRs and normotensive Wistar Kyoto rats (WKYs) fed a purified diet, as well as SHRs consuming a grain-based chow (GBC) diet.
Results
SHRs on a purified diet, but not WKYs or SHRs consuming GBC, exhibited impaired coronary flow reserve as assessed by echocardiography. This occurred despite the persistence of hypertension in SHRs irrespective of diet.
Conclusions
SHRs develop a diet-dependent CMD, which can serve as a model to study hypertension-related CMD.
{"title":"An Animal Model of Coronary Microvascular Dysfunction (CMD) in the Female Spontaneously Hypertensive Rat: The Role of Diet","authors":"Rami S. Najjar, Puja K. Mehta, Andrew T. Gewirtz","doi":"10.1111/micc.70052","DOIUrl":"10.1111/micc.70052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Coronary microvascular dysfunction (CMD) drives angina in patients with ischemia with non-obstructive coronary artery disease, a condition that is more prevalent in females. Effective treatment strategies remain limited, in part, due to the scarcity of physiologically relevant animal models. Indeed, while CMD has been studied in animals with diabetes or fed high-fat diets, hypertension is the predominant risk factor for CMD in humans, but is not captured by these models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We characterized the CMD that arose in female spontaneously hypertensive rats (SHRs). We measured coronary flow reserve, alongside basic cardiovascular function in SHRs and normote<b>n</b>sive Wistar Kyoto rats (WKYs) fed a purified diet, as well as SHRs consuming a grain-based chow (GBC) diet.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SHRs on a purified diet, but not WKYs or SHRs consuming GBC, exhibited impaired coronary flow reserve as assessed by echocardiography. This occurred despite the persistence of hypertension in SHRs irrespective of diet.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SHRs develop a diet-dependent CMD, which can serve as a model to study hypertension-related CMD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052833","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}
Erin Zhao, Jared Barber, Shomita S. Mathew-Steiner, Savita Khanna, Chandan K. Sen, Julia Arciero
Objective
This study demonstrates the impact of alterations in pressure, vascular compliance, arterial pulsatility, and autoregulation on tissue perfusion following middle cerebral artery (MCA) occlusion using mathematical modeling.
Methods
Our previous mathematical model of the cerebral circulation is expanded to include vessel compliance and pulsatility of blood flow. An experimentally-obtained pressure waveform is used as an incoming boundary condition to simulate the effects of vascular compliance and pulsatility of flow on perfusion following MCA occlusion. The waveform is adjusted to model the effects of elevated mean arterial pressure.
Results
Increased distensibility reduces the amplitude of oscillations in the time-dependent pressure solutions, whereas decreased distensibility produces more variation in these pressures. Occlusion significantly alters the magnitude of flow changes when incoming pressure is varied. The addition of the pulsatile pressure boundary condition and capacitances in the arteries and veins shifts the autoregulation plateau to higher pressures.
Conclusions
This study reveals how changes in incoming pressure affect compensatory responses to ischemic stroke caused by MCA occlusion. Boundary conditions corresponding to elevated mean arterial pressures are associated with lower degrees of ischemia, an improvement that is supported by changes in autoregulation patterns following occlusion. The results also demonstrate how increases in arterial stiffness associated with aging can inhibit the ability of the vasculature to accommodate pulsatile flow by analyzing resulting patterns such as larger amplitudes of pressure and flow oscillations in the microcirculation. The study provides a foundation for modeling the relationships among vessel compliance, arterial blood pressure, and cerebrovascular conditions.
{"title":"Modeling Pressure-Dependent Wave and Vessel Compliance in the Brain Following Middle Cerebral Artery Occlusion","authors":"Erin Zhao, Jared Barber, Shomita S. Mathew-Steiner, Savita Khanna, Chandan K. Sen, Julia Arciero","doi":"10.1111/micc.70049","DOIUrl":"10.1111/micc.70049","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study demonstrates the impact of alterations in pressure, vascular compliance, arterial pulsatility, and autoregulation on tissue perfusion following middle cerebral artery (MCA) occlusion using mathematical modeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Our previous mathematical model of the cerebral circulation is expanded to include vessel compliance and pulsatility of blood flow. An experimentally-obtained pressure waveform is used as an incoming boundary condition to simulate the effects of vascular compliance and pulsatility of flow on perfusion following MCA occlusion. The waveform is adjusted to model the effects of elevated mean arterial pressure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Increased distensibility reduces the amplitude of oscillations in the time-dependent pressure solutions, whereas decreased distensibility produces more variation in these pressures. Occlusion significantly alters the magnitude of flow changes when incoming pressure is varied. The addition of the pulsatile pressure boundary condition and capacitances in the arteries and veins shifts the autoregulation plateau to higher pressures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study reveals how changes in incoming pressure affect compensatory responses to ischemic stroke caused by MCA occlusion. Boundary conditions corresponding to elevated mean arterial pressures are associated with lower degrees of ischemia, an improvement that is supported by changes in autoregulation patterns following occlusion. The results also demonstrate how increases in arterial stiffness associated with aging can inhibit the ability of the vasculature to accommodate pulsatile flow by analyzing resulting patterns such as larger amplitudes of pressure and flow oscillations in the microcirculation. The study provides a foundation for modeling the relationships among vessel compliance, arterial blood pressure, and cerebrovascular conditions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12835686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052849","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}
Luis A. Pardo Jr., Charlotte Brinkmeyer, Meike A. Wilke, Lisa Lorbeer, Marc Varel, Arndt F. Schilling, Jennifer Ernst
Objective
Skin integrity is one factor determining residual limb health. Oxygen deficiency caused by energy consumption and/or mechanical stress is the most common reason for skin breakdown at the residual limb (RL), limiting physical activity and causing residual limb pain (RLP). This study aims to detect differences in microcirculation at rest (T1) and after walking for 6 min (T2) with a socket prosthesis at different zones at the residual limb (RL) and the corresponding areas at the sound limb (SL).
Methods
Amputation and RLs' demographics as limb circumference (LCF), subcutaneous fat thickness (SCFT) and microcirculatory parameters as tissue oxygenation saturation (StO2), near-infrared perfusion index (NIRPI), tissue hemoglobin index (THI) and tissue water index (TWI) were visualized and analyzed at different zones of the SL and RL of ten non-dysvascular major lower limb amputees at T1 and T2 using ((HIS), TIVITA Tissue Diaspective Vision, Germany).
Results
LCF and SCFT were lower at the RL than at the SL. A significant reduction of NIRPI after walking was observed at location F2, affecting both limbs. StO2 decreased significantly from T1 to T2 only at the residual limb at AL, with no corresponding change in the sound limb.
Discussion
These findings demonstrate localized exercise-related reductions in oxygenation at the distal RL, whereas microcirculation of the SL remained unchanged. Underlying factors and a possible impact on the overall residual limb health need further investigation.
{"title":"Hyperspectral Imaging Reveals High Water and Hemoglobin Content at Rest and Decreased Oxygen Levels After Physical Activity at the Residual Limb of Non-Dysvascular Lower Limb Amputees","authors":"Luis A. Pardo Jr., Charlotte Brinkmeyer, Meike A. Wilke, Lisa Lorbeer, Marc Varel, Arndt F. Schilling, Jennifer Ernst","doi":"10.1111/micc.70051","DOIUrl":"10.1111/micc.70051","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Skin integrity is one factor determining residual limb health. Oxygen deficiency caused by energy consumption and/or mechanical stress is the most common reason for skin breakdown at the residual limb (RL), limiting physical activity and causing residual limb pain (RLP). This study aims to detect differences in microcirculation at rest (T1) and after walking for 6 min (T2) with a socket prosthesis at different zones at the residual limb (RL) and the corresponding areas at the sound limb (SL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Amputation and RLs' demographics as limb circumference (LCF), subcutaneous fat thickness (SCFT) and microcirculatory parameters as tissue oxygenation saturation (StO<sub>2</sub>), near-infrared perfusion index (NIRPI), tissue hemoglobin index (THI) and tissue water index (TWI) were visualized and analyzed at different zones of the SL and RL of ten non-dysvascular major lower limb amputees at T1 and T2 using ((HIS), TIVITA Tissue Diaspective Vision, Germany).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LCF and SCFT were lower at the RL than at the SL. A significant reduction of NIRPI after walking was observed at location F2, affecting both limbs. StO<sub>2</sub> decreased significantly from T1 to T2 only at the residual limb at AL, with no corresponding change in the sound limb.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Discussion</h3>\u0000 \u0000 <p>These findings demonstrate localized exercise-related reductions in oxygenation at the distal RL, whereas microcirculation of the SL remained unchanged. Underlying factors and a possible impact on the overall residual limb health need further investigation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998082","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}
Song Yao, Tianfu Fu, Qingxian Tu, Jie Zhang, Qianfeng Jiang, Min Xu, Zhenglong Wang, Yang Jiao, Haixia Tian
Background
Salt-sensitive hypertension (SSH) is associated with phenotypic changes in vascular smooth muscle cells (VSMCs). This study aimed to investigate the role of interleukin-17 (IL-17) in SSH and its impact on VSMC phenotype, focusing on the PI3K/AKT signaling pathway.
Methods
In vivo, an SSH rat model was established. Systolic blood pressure (SBP) was monitored, and mesenteric artery tissues were collected for ex vivo histological and immunohistochemical analysis. In vitro, VSMCs were isolated from the arteries. Lentiviral vectors were used to knock down or overexpress IL-17 in these cells. Cell viability, migration, and invasion were assessed using CCK-8, scratch, and Transwell assays, respectively. Phosphorylation status was analyzed using a RayBiotech antibody array. Protein expression and phosphorylation levels were analyzed by Western blotting.
Results
In vivo, SSH model rats developed hypertension and exhibited VSMC phenotypic transformation in mesenteric arteries. In vitro, VSMCs from SSH model rats showed elevated IL-17 expression. Knockdown of IL-17 in these cells suppressed their hyper-proliferative, migratory, and invasive phenotype and reversed the expression changes of contractile (α-actin and calponin) and synthetic (osteopontin) markers. This was associated with inhibition of PI3K/AKT phosphorylation. Conversely, IL-17 overexpression in control VSMCs recapitulated the pathological phenotype, which was blocked by the PI3K/AKT inhibitor Wortmannin (WM).
Conclusion
IL-17 promotes the phenotypic transformation of VSMCs in SSH through the PI3K/AKT signaling pathway. Inhibition of IL-17 or the PI3K/AKT pathway may represent a therapeutic strategy for SSH.
{"title":"IL-17 Promotes the Phenotypic Transformation of Vascular Smooth Muscle Cells Through PI3K/AKT Signaling Pathway","authors":"Song Yao, Tianfu Fu, Qingxian Tu, Jie Zhang, Qianfeng Jiang, Min Xu, Zhenglong Wang, Yang Jiao, Haixia Tian","doi":"10.1111/micc.70050","DOIUrl":"10.1111/micc.70050","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Salt-sensitive hypertension (SSH) is associated with phenotypic changes in vascular smooth muscle cells (VSMCs). This study aimed to investigate the role of interleukin-17 (IL-17) in SSH and its impact on VSMC phenotype, focusing on the PI3K/AKT signaling pathway.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vivo, an SSH rat model was established. Systolic blood pressure (SBP) was monitored, and mesenteric artery tissues were collected for ex vivo histological and immunohistochemical analysis. In vitro, VSMCs were isolated from the arteries. Lentiviral vectors were used to knock down or overexpress IL-17 in these cells. Cell viability, migration, and invasion were assessed using CCK-8, scratch, and Transwell assays, respectively. Phosphorylation status was analyzed using a RayBiotech antibody array. Protein expression and phosphorylation levels were analyzed by Western blotting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In vivo, SSH model rats developed hypertension and exhibited VSMC phenotypic transformation in mesenteric arteries. In vitro, VSMCs from SSH model rats showed elevated IL-17 expression. Knockdown of IL-17 in these cells suppressed their hyper-proliferative, migratory, and invasive phenotype and reversed the expression changes of contractile (α-actin and calponin) and synthetic (osteopontin) markers. This was associated with inhibition of PI3K/AKT phosphorylation. Conversely, IL-17 overexpression in control VSMCs recapitulated the pathological phenotype, which was blocked by the PI3K/AKT inhibitor Wortmannin (WM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>IL-17 promotes the phenotypic transformation of VSMCs in SSH through the PI3K/AKT signaling pathway. Inhibition of IL-17 or the PI3K/AKT pathway may represent a therapeutic strategy for SSH.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998154","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}
Philippe Guerci, Can Ince, Olcay Dilken, Thibaut Belveyre, Coline Lapoix, Jonathan Montomoli, Matthias P. Hilty
Objective
Handheld vital microscopy (HVM) enables bedside visualization of the microcirculation, with major improvements from sidestream darkfield (SDF) to incident dark field (IDF) imaging. Although IDF offers high-resolution images, standard analysis methods require down-sampling to match SDF's lower field of view (FOV) and pixel density. MicroTools, an automated stabilization and analysis algorithm, has previously been validated for use with SDF image sequences. This study aimed to assess the accuracy and precision of microcirculatory analysis using MicroTools on full-frame, high-resolution IDF images.
Methods
Image sequences from a previous study were re-analyzed in both IDF and down-sampled SDF formats. Microcirculatory parameters—including total vessel density (TVD), functional capillary density, and red blood cell velocity (RBCv)—were compared between formats. MicroTools' new stabilization algorithm was also evaluated against existing algorithms.
Results
Full-frame IDF analysis increased the FOV by 200% and pixel density by 66%, enhancing capillary detection and TVD measurements. RBCv values were lower with IDF images. The updated stabilization algorithm showed performance comparable to prior methods.
Conclusions
MicroTools analysis of full-frame IDF images improved measurement accuracy and vessel detection, with excellent agreement to standard software. Its new stabilization algorithm proved equally robust, supporting broader adoption in clinical research.
{"title":"Improved Detection of Capillaries in High-Resolution Handheld Vital Microscopy by Use of the MicroTools Advanced Computer Vision Algorithm","authors":"Philippe Guerci, Can Ince, Olcay Dilken, Thibaut Belveyre, Coline Lapoix, Jonathan Montomoli, Matthias P. Hilty","doi":"10.1111/micc.70045","DOIUrl":"10.1111/micc.70045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Handheld vital microscopy (HVM) enables bedside visualization of the microcirculation, with major improvements from sidestream darkfield (SDF) to incident dark field (IDF) imaging. Although IDF offers high-resolution images, standard analysis methods require down-sampling to match SDF's lower field of view (FOV) and pixel density. MicroTools, an automated stabilization and analysis algorithm, has previously been validated for use with SDF image sequences. This study aimed to assess the accuracy and precision of microcirculatory analysis using MicroTools on full-frame, high-resolution IDF images.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Image sequences from a previous study were re-analyzed in both IDF and down-sampled SDF formats. Microcirculatory parameters—including total vessel density (TVD), functional capillary density, and red blood cell velocity (RBCv)—were compared between formats. MicroTools' new stabilization algorithm was also evaluated against existing algorithms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Full-frame IDF analysis increased the FOV by 200% and pixel density by 66%, enhancing capillary detection and TVD measurements. RBCv values were lower with IDF images. The updated stabilization algorithm showed performance comparable to prior methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MicroTools analysis of full-frame IDF images improved measurement accuracy and vessel detection, with excellent agreement to standard software. Its new stabilization algorithm proved equally robust, supporting broader adoption in clinical research.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.70045","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900764","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}
Xiaoxi Sun, Xiang Fang, Ying Fang, Jianhua Wu, Jiangguo Lin
Background
Circulating tumor cells (CTCs) utilize platelets to withstand hemodynamic stress and evade immune clearance; however, the mechanisms driving platelet–cancer cell aggregation under flow remain unclear.
Objective
We investigated which physical quantity—shear rate, exposure time, or an integrated metric—governs the aggregation and identified the key adhesion molecules involved.
Methods
Human platelets and EGFR-mutant lung adenocarcinoma PC-9 cells were fluorescently labeled, mixed at a 10:1 ratio, and subjected to mechanical stimulation using a vortex mixer or a TA ARES G2 rheometer across shear rates 0–4050 s−1 and durations of 0–4860 s. Aggregates were quantified by flow cytometry via dual-positive gating. The functional roles of platelet P-selectin and CD40 ligand (CD40L) were assessed using antibodies Inclacumab and 5c8, respectively. Shear significantly promoted platelet–PC-9 aggregation compared with static conditions, while blocking P-selectin or CD40L markedly suppressed this effect.
Results
Aggregation exhibited a biphasic dependence on both shear rate and exposure time. Notably, when plotting aggregation against shear accumulation (rate × time), all data converged onto a unified biphasic curve with an optimum of ~27 000.
Conclusions
These results indicate that platelet–PC-9 aggregation is governed by a shear accumulation–dependent mechanism, optimized under moderate shear and finite exposure, and regulated by P-selectin and CD40L. These findings provide new biophysical insights into transient platelet-PC-9 interactions in circulation and suggest that targeting platelet activation pathways or modulating hemodynamics may prevent hematogenous metastasis.
背景：循环肿瘤细胞（CTCs）利用血小板承受血流动力学压力并逃避免疫清除；然而，驱动血小板癌细胞在流动下聚集的机制仍不清楚。目的：我们研究了哪些物理量——剪切速率、暴露时间或一个综合指标——控制了聚集，并确定了涉及的关键粘附分子。方法：对人血小板和egfr突变肺腺癌PC-9细胞进行荧光标记，以10:1的比例混合，并使用涡旋混合器或TA ARES G2流变仪进行机械刺激，剪切速率为0-4050 s-1，持续时间为0-4860 s。双阳性门控流式细胞术定量聚集体。分别使用抗体Inclacumab和5c8评估血小板p -选择素和CD40配体（CD40L）的功能作用。与静态条件相比，剪切显著促进血小板- pc -9聚集，而阻断p -选择素或CD40L则明显抑制这一作用。结果：聚合表现为剪切速率和暴露时间的双相依赖性。值得注意的是，当绘制聚集与剪切积累（速率×时间）的关系时，所有数据都收敛到统一的双相曲线上，最优值为~ 27000。结论：这些结果表明血小板- pc -9聚集受剪切积累依赖机制控制，在中等剪切和有限暴露条件下优化，并受p -选择素和CD40L调控。这些发现为血液循环中血小板与pc -9的短暂相互作用提供了新的生物物理学见解，并表明靶向血小板激活途径或调节血流动力学可能预防血液转移。
{"title":"Aggregation of Platelets and Human EGFR Mutant Lung Adenocarcinoma Cells Under Flow Is Governed by Shear Accumulation","authors":"Xiaoxi Sun, Xiang Fang, Ying Fang, Jianhua Wu, Jiangguo Lin","doi":"10.1111/micc.70047","DOIUrl":"10.1111/micc.70047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Circulating tumor cells (CTCs) utilize platelets to withstand hemodynamic stress and evade immune clearance; however, the mechanisms driving platelet–cancer cell aggregation under flow remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We investigated which physical quantity—shear rate, exposure time, or an integrated metric—governs the aggregation and identified the key adhesion molecules involved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human platelets and EGFR-mutant lung adenocarcinoma PC-9 cells were fluorescently labeled, mixed at a 10:1 ratio, and subjected to mechanical stimulation using a vortex mixer or a TA ARES G2 rheometer across shear rates 0–4050 s<sup>−1</sup> and durations of 0–4860 s. Aggregates were quantified by flow cytometry via dual-positive gating. The functional roles of platelet P-selectin and CD40 ligand (CD40L) were assessed using antibodies Inclacumab and 5c8, respectively. Shear significantly promoted platelet–PC-9 aggregation compared with static conditions, while blocking P-selectin or CD40L markedly suppressed this effect.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Aggregation exhibited a biphasic dependence on both shear rate and exposure time. Notably, when plotting aggregation against shear accumulation (rate × time), all data converged onto a unified biphasic curve with an optimum of ~27 000.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results indicate that platelet–PC-9 aggregation is governed by a shear accumulation–dependent mechanism, optimized under moderate shear and finite exposure, and regulated by P-selectin and CD40L. These findings provide new biophysical insights into transient platelet-PC-9 interactions in circulation and suggest that targeting platelet activation pathways or modulating hemodynamics may prevent hematogenous metastasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145863477","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}
To determine whether androgen deprivation therapy (ADT) alters laser speckle flowgraphy (LSFG)-detectable choroidal microvascular dynamics: mean blur rate (MBR, blood flow) and beat strength over MBR (BOM, microvascular resistance). We also investigated whether such changes emerge even when cardio-ankle vascular index (CAVI)-assessed large-artery stiffness remains unchanged.
Methods
This study included 17 right eyes of 17 men with prostate cancer. Serum testosterone, CAVI, and choroidal parameters (MBR, BOM) were obtained at baseline and 6 months post-ADT. Central choroidal thickness (CCT) and ocular perfusion pressure (OPP) were also recorded.
Results
Serum testosterone significantly decreased (4.45 ± 1.96 to 0.20 ± 0.08 ng/mL; p < 0.001) after 6 months. Choroidal BOM increased significantly (0.94 ± 0.31 to 1.11 ± 0.31; p = 0.028), whereas CAVI (10.70 ± 1.28 to 10.68 ± 1.19), choroidal MBR (8.46 ± 4.50 to 7.89 ± 3.48), CCT, and OPP did not change significantly.
Conclusion
Choroidal BOM increased significantly during the initial 6 months of ADT, indicating higher microvascular resistance despite stable choroidal blood flow and unchanged large artery stiffness. This supports a “microcirculation-first” model. LSFG-derived BOM may serve as a biomarker for early detection and monitoring of microcirculatory dysfunction under systemic testosterone suppression.
{"title":"Impact of Androgen Deprivation Therapy on Choroidal Microcirculation Assessed Using Laser Speckle Flowgraphy","authors":"Ryuya Hashimoto, Ryo Oka, Naoki Fujioka, Kazufumi Tanaka, Moe Nunose, Sara Imai, Ryota Takenaka, Takahide Noro, Takatoshi Somoto, Takanobu Utsumi, Naoto Kamiya, Fumihiko Yagi, Hiroyoshi Suzuki","doi":"10.1111/micc.70048","DOIUrl":"10.1111/micc.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine whether androgen deprivation therapy (ADT) alters laser speckle flowgraphy (LSFG)-detectable choroidal microvascular dynamics: mean blur rate (MBR, blood flow) and beat strength over MBR (BOM, microvascular resistance). We also investigated whether such changes emerge even when cardio-ankle vascular index (CAVI)-assessed large-artery stiffness remains unchanged.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study included 17 right eyes of 17 men with prostate cancer. Serum testosterone, CAVI, and choroidal parameters (MBR, BOM) were obtained at baseline and 6 months post-ADT. Central choroidal thickness (CCT) and ocular perfusion pressure (OPP) were also recorded.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Serum testosterone significantly decreased (4.45 ± 1.96 to 0.20 ± 0.08 ng/mL; <i>p</i> < 0.001) after 6 months. Choroidal BOM increased significantly (0.94 ± 0.31 to 1.11 ± 0.31; <i>p</i> = 0.028), whereas CAVI (10.70 ± 1.28 to 10.68 ± 1.19), choroidal MBR (8.46 ± 4.50 to 7.89 ± 3.48), CCT, and OPP did not change significantly.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Choroidal BOM increased significantly during the initial 6 months of ADT, indicating higher microvascular resistance despite stable choroidal blood flow and unchanged large artery stiffness. This supports a “microcirculation-first” model. LSFG-derived BOM may serve as a biomarker for early detection and monitoring of microcirculatory dysfunction under systemic testosterone suppression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145856850","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}
Current research on the lymphatic system makes nearly exclusive use of mouse models because that species is highly amenable to genetic manipulation. However, the lack of information about intraluminal hydrostatic pressures in mouse lymphatic networks limits the ability of investigators, for both in vivo and ex vivo studies, to interpret key physiological data. The goal of the present study was to provide some of that information for several commonly studied lymphatic vessel networks of young, healthy mice: the superficial cervical lymphatic network, the popliteal afferent network, and the mesentery network.
Methods
The servo-null micropressure method was used to measure intraluminal hydrostatic pressures in lymphatic vessels, taking advantage of Prox1-GFP and Prox1-tom mice, expressing eGFP and td-tomato reporters, respectively, in lymphatic endothelium, to visualize entire lymphatic networks and facilitate micropuncture of individual vessels.
Results
New methods were devised for making servo-null pressure measurements under fluorescence illumination. Intraluminal pressures oscillated with the lymphatic contraction cycle, and systolic pressure peaks coincided with lymphatic systole. The largest peaks occurred when contractions of consecutive lymphangions were entrained. In networks with active contractions, the pressure profile was “uphill”; in networks without contractions, the pressure profile was “downhill.”
Conclusions
Our results provide essential information about the “normal” values for intraluminal hydrostatic pressures in several of the most commonly studied lymphatic networks of the mouse.
{"title":"Hydrostatic Pressures in Lymphatic Networks of the Mouse","authors":"Michael J. Davis","doi":"10.1111/micc.70046","DOIUrl":"10.1111/micc.70046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Current research on the lymphatic system makes nearly exclusive use of mouse models because that species is highly amenable to genetic manipulation. However, the lack of information about intraluminal hydrostatic pressures in mouse lymphatic networks limits the ability of investigators, for both in vivo and ex vivo studies, to interpret key physiological data. The goal of the present study was to provide some of that information for several commonly studied lymphatic vessel networks of young, healthy mice: the superficial cervical lymphatic network, the popliteal afferent network, and the mesentery network.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The servo-null micropressure method was used to measure intraluminal hydrostatic pressures in lymphatic vessels, taking advantage of <i>Prox1-GFP</i> and <i>Prox1-tom</i> mice, expressing eGFP and td-tomato reporters, respectively, in lymphatic endothelium, to visualize entire lymphatic networks and facilitate micropuncture of individual vessels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>New methods were devised for making servo-null pressure measurements under fluorescence illumination. Intraluminal pressures oscillated with the lymphatic contraction cycle, and systolic pressure peaks coincided with lymphatic systole. The largest peaks occurred when contractions of consecutive lymphangions were entrained. In networks with active contractions, the pressure profile was “uphill”; in networks without contractions, the pressure profile was “downhill.”</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results provide essential information about the “normal” values for intraluminal hydrostatic pressures in several of the most commonly studied lymphatic networks of the mouse.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12714131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781344","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}
Milena Esposito, Sarah M. Tremble, Marilyn J. Cipolla
Objective
We examined if exposure to experimental preeclampsia (ePE) impacts vascular permeability and reactivity of posterior cerebral arteries (PCAs) in adult offspring, and if maternal antioxidant treatment prevents these effects in adult male and female offspring.
Methods
Offspring (F1) from rats with Normal pregnancy (NormPreg_F1), ePE_F1 and ePE treated with apocynin (ePE + apo_F1) were weighed at p24, p31, p38, and p45. Maternal apocynin was administered weekly in drinking water at a dose of ∼24 mg/kg (3 mM) on gestational days 11–20. Blood–brain barrier (BBB) permeability, structure and function of PCAs were measured from male and female adult offspring (n = 8/group, 12–29 weeks). Circulating inflammatory factors were measured by multiplex array.
Results
Male ePE_F1 had smaller body weights than male NormPreg_F1 (p < 0.05) at all ages which was prevented by maternal apocynin. Female ePE_F1 body weights were less only at p24 which was prevented by maternal apocynin. PCAs from male ePE_F1 had increased BBB permeability versus male NormPreg_F1 which was prevented by apocynin (p < 0.05). These changes were not seen in female ePE_F1s. Maternal ePE did not affect PCA reactivity to inward potassium rectifier channel or voltage-operated calcium channel activation, nor reactivity to L-NAME and sodium nitroprusside. There were little differences in plasma inflammatory factors.
Conclusions
ePE exposure had long-term consequences on the cerebral circulation of adult male offspring. Understanding the underlying mechanism by which PE adversely impacts the brain of offspring may lead to the prevention of cognitive decline and stroke in adulthood.
{"title":"Maternal Apocynin During Experimental Preeclampsia Prevents BBB Permeability and Increased Vascular Tone of Cerebral Arteries in Male but Not Female Rat Adult Offspring","authors":"Milena Esposito, Sarah M. Tremble, Marilyn J. Cipolla","doi":"10.1111/micc.70044","DOIUrl":"10.1111/micc.70044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We examined if exposure to experimental preeclampsia (ePE) impacts vascular permeability and reactivity of posterior cerebral arteries (PCAs) in adult offspring, and if maternal antioxidant treatment prevents these effects in adult male and female offspring.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Offspring (F1) from rats with Normal pregnancy (NormPreg_F1), ePE_F1 and ePE treated with apocynin (ePE + apo_F1) were weighed at p24, p31, p38, and p45. Maternal apocynin was administered weekly in drinking water at a dose of ∼24 mg/kg (3 mM) on gestational days 11–20. Blood–brain barrier (BBB) permeability, structure and function of PCAs were measured from male and female adult offspring (<i>n</i> = 8/group, 12–29 weeks). Circulating inflammatory factors were measured by multiplex array.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Male ePE_F1 had smaller body weights than male NormPreg_F1 (<i>p</i> < 0.05) at all ages which was prevented by maternal apocynin. Female ePE_F1 body weights were less only at p24 which was prevented by maternal apocynin. PCAs from male ePE_F1 had increased BBB permeability versus male NormPreg_F1 which was prevented by apocynin (<i>p</i> < 0.05). These changes were not seen in female ePE_F1s. Maternal ePE did not affect PCA reactivity to inward potassium rectifier channel or voltage-operated calcium channel activation, nor reactivity to L-NAME and sodium nitroprusside. There were little differences in plasma inflammatory factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ePE exposure had long-term consequences on the cerebral circulation of adult male offspring. Understanding the underlying mechanism by which PE adversely impacts the brain of offspring may lead to the prevention of cognitive decline and stroke in adulthood.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12710456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768521","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}
Amanda E. Wietrzny, Austen R. Schweinert, Gabriel R. Merkow, Jennifer N. Nguyen, Alicen A. Whitaker-Hilbig, Allison S. Hyngstrom, Matthew J. Durand
Objective and Hypothesis
Cutaneous microvascular reactivity was investigated in chronic stroke survivors by comparing vasodilatory responses in the paretic and non-paretic legs to matched controls. It was hypothesized that vasodilatory responses would be blunted in the paretic leg of stroke survivors vs. the non-paretic leg and controls.
Methods
Cutaneous vascular conductance to local heating was measured in 20 stroke survivors and 20 controls using laser-Doppler flowmetry probes with integrated heaters. Probes were placed on both legs of stroke survivors and the dominant leg of controls. After 15 min rest, the skin was subjected to gradual (1°C/5 min) or rapid heating (0.1°C/s) to 39°C, then increased to 43°C to induce maximal vasodilation.
Results
Vasodilation to gradual heating did not differ between the paretic and non-paretic legs of stroke survivors (p = 0.07) and controls (p = 0.82). Neurogenic axon-mediated responses to rapid heating showed no differences across groups (paretic vs. non-paretic, p = 1.00; paretic vs. control, p = 0.23).
Conclusion
Cutaneous vasodilatory responses to gradual and rapid heating were comparable between stroke survivors and controls. Future studies combining local heating with dermal microdialysis should explore specific vasodilatory pathways, as limb-specific changes may not be evident by measuring vasodilatory magnitude alone.
{"title":"Microvascular Reactivity to Cutaneous Local Heating in the Paretic and Non-Paretic Legs of Chronic Stroke Survivors—A Pilot Study","authors":"Amanda E. Wietrzny, Austen R. Schweinert, Gabriel R. Merkow, Jennifer N. Nguyen, Alicen A. Whitaker-Hilbig, Allison S. Hyngstrom, Matthew J. Durand","doi":"10.1111/micc.70036","DOIUrl":"10.1111/micc.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective and Hypothesis</h3>\u0000 \u0000 <p>Cutaneous microvascular reactivity was investigated in chronic stroke survivors by comparing vasodilatory responses in the paretic and non-paretic legs to matched controls. It was hypothesized that vasodilatory responses would be blunted in the paretic leg of stroke survivors vs. the non-paretic leg and controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cutaneous vascular conductance to local heating was measured in 20 stroke survivors and 20 controls using laser-Doppler flowmetry probes with integrated heaters. Probes were placed on both legs of stroke survivors and the dominant leg of controls. After 15 min rest, the skin was subjected to gradual (1°C/5 min) or rapid heating (0.1°C/s) to 39°C, then increased to 43°C to induce maximal vasodilation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Vasodilation to gradual heating did not differ between the paretic and non-paretic legs of stroke survivors (<i>p</i> = 0.07) and controls (<i>p</i> = 0.82). Neurogenic axon-mediated responses to rapid heating showed no differences across groups (paretic vs. non-paretic, <i>p</i> = 1.00; paretic vs. control, <i>p</i> = 0.23).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Cutaneous vasodilatory responses to gradual and rapid heating were comparable between stroke survivors and controls. Future studies combining local heating with dermal microdialysis should explore specific vasodilatory pathways, as limb-specific changes may not be evident by measuring vasodilatory magnitude alone.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"33 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768452","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}
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