Mohammad Jamshidi, Thomas Ventimiglia, Patrice Sudres, Cong Zhang, Frédéric Lesage, William Rooney, Daniel Schwartz, Andreas A. Linninger
Objective
The role of cerebral microvasculature in cognitive dysfunction can be investigated by identifying the impact of blood flow on cortical tissue oxygenation. In this paper, the impact of capillary stalls on microcirculatory characteristics such as flow and hematocrit (Ht) in the cortical angioarchitecture is studied.
Methods
Using a deterministic mathematical model to simulate blood flow in a realistic mouse cortex, hemodynamics parameters, including pressure, flow, vessel diameter-adjustable hematocrit, and transit time are calculated as a function of stalling events.
Results
Using a non-linear plasma skimming model, it is observed that Ht increases in the penetrating arteries from the pial vessels as a function of cortical depth. The incidence of stalling on Ht distribution along the blood network vessels shows reduction of RBCs around the tissue near occlusion sites and decreased Ht concentration downstream from the blockage points. Moreover, upstream of the occlusion, there is a noticeable increase of the Ht, leading to larger flow resistance due to higher blood viscosity. We predicted marked changes in transit time behavior due to stalls which match trends observed in mice in vivo.
Conclusions
These changes to blood cell quantity and quality may be implicated in the development of Alzheimer's disease and contribute to the course of the illness.
{"title":"Impact of stalling events on microcirculatory hemodynamics in the aged brain","authors":"Mohammad Jamshidi, Thomas Ventimiglia, Patrice Sudres, Cong Zhang, Frédéric Lesage, William Rooney, Daniel Schwartz, Andreas A. Linninger","doi":"10.1111/micc.12845","DOIUrl":"10.1111/micc.12845","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The role of cerebral microvasculature in cognitive dysfunction can be investigated by identifying the impact of blood flow on cortical tissue oxygenation. In this paper, the impact of capillary stalls on microcirculatory characteristics such as flow and hematocrit (Ht) in the cortical angioarchitecture is studied.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Using a deterministic mathematical model to simulate blood flow in a realistic mouse cortex, hemodynamics parameters, including pressure, flow, vessel diameter-adjustable hematocrit, and transit time are calculated as a function of stalling events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Using a non-linear plasma skimming model, it is observed that Ht increases in the penetrating arteries from the pial vessels as a function of cortical depth. The incidence of stalling on Ht distribution along the blood network vessels shows reduction of RBCs around the tissue near occlusion sites and decreased Ht concentration downstream from the blockage points. Moreover, upstream of the occlusion, there is a noticeable increase of the Ht, leading to larger flow resistance due to higher blood viscosity. We predicted marked changes in transit time behavior due to stalls which match trends observed in mice in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These changes to blood cell quantity and quality may be implicated in the development of Alzheimer's disease and contribute to the course of the illness.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12845","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542533","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}
Rebekka Heitmar, Paulus Kirchhoff, Andrew Blann, Konstantin Kotliar
Objective
We aimed to characterize several aspects of retinal vascular dynamics in a patient with arrythmia in order to elicit additional diagnostic information on microvascular dysfunction.
Methods
A 68-year-old male patient with arrythmia and an age- and gender-matched control subject underwent ocular examination including dynamic retinal vessel assessment with flicker light provocation. Retinal vessel diameters were measured continuously following a standard protocol (IMEDOS Systems, Jena, Germany). The data were evaluated using methods of signal analysis.
Results
Retinal vessel response following flicker provocation as well as local structural and functional behavior of retinal vessels were comparable between both individuals. The arrhythmia case demonstrated irregular arterial and venous heart rate (HR) pulsation with an average frequency of 1 Hz. Moreover, the case showed a higher magnitude and larger periods of low-frequency retinal vessel oscillations as well as lower periodicity of both HR pulsations and low-frequency vasomotions.
Conclusions
Besides numerical examination of irregular HR pulsations in case of arrhythmia, from the direct noninvasive assessment of retinal vessel dynamics one can derive more detailed information on microvascular function including the whole spectrum of retinal arterial and venous pulsations and vasomotions. This may have implications for health screening not limited to atrial fibrillation.
我们的目的是描述一名心律失常患者视网膜血管动态的几个方面，以获得有关微血管功能障碍的更多诊断信息。
{"title":"Retinal vascular dynamics: A window for observing an irregular heartbeat. A case report","authors":"Rebekka Heitmar, Paulus Kirchhoff, Andrew Blann, Konstantin Kotliar","doi":"10.1111/micc.12844","DOIUrl":"10.1111/micc.12844","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We aimed to characterize several aspects of retinal vascular dynamics in a patient with arrythmia in order to elicit additional diagnostic information on microvascular dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A 68-year-old male patient with arrythmia and an age- and gender-matched control subject underwent ocular examination including dynamic retinal vessel assessment with flicker light provocation. Retinal vessel diameters were measured continuously following a standard protocol (IMEDOS Systems, Jena, Germany). The data were evaluated using methods of signal analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Retinal vessel response following flicker provocation as well as local structural and functional behavior of retinal vessels were comparable between both individuals. The arrhythmia case demonstrated irregular arterial and venous heart rate (HR) pulsation with an average frequency of 1 Hz. Moreover, the case showed a higher magnitude and larger periods of low-frequency retinal vessel oscillations as well as lower periodicity of both HR pulsations and low-frequency vasomotions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Besides numerical examination of irregular HR pulsations in case of arrhythmia, from the direct noninvasive assessment of retinal vessel dynamics one can derive more detailed information on microvascular function including the whole spectrum of retinal arterial and venous pulsations and vasomotions. This may have implications for health screening not limited to atrial fibrillation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139495613","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}
Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD.
Methods
We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO2, O2 pulse trajectory, and exercise ECG test.
Results
Men with NOCAD had significantly lower predicted % peak VO2 (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O2 pulse trajectory (2% vs. 0%) (p < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O2 pulse trajectory (21% vs. 6%, p < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, p < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO2 (β −27.4, 95% CI −30.74 to −24.07), higher risk for abnormal O2 pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (p < .0001).
Conclusion
Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.
{"title":"Men with nonobstructive coronary disease have higher burden of ischemic heart disease detected by cardiopulmonary exercise test","authors":"Siyuan Li, Yifang Yuan, Lanting Zhao, Tingting Lv, Fei She, Fang Liu, Yajun Xue, Boda Zhou, Ying Xie, Yu Geng, Ping Zhang","doi":"10.1111/micc.12841","DOIUrl":"10.1111/micc.12841","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nonobstructive coronary artery disease (NOCAD), characterized by the presence of myocardial ischemic symptoms and signs without obstructive coronaries, is a common clinical condition, but it is less well understood. Few studies have analyzed the gender differences in inducible myocardial ischemia assessed by cardiopulmonary exercise test (CPET) in NOCAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a study of 289 NOCAD patients (mean age 60, 56% women) with ischemic symptoms and confirmed ⫹50% coronaries stenoses by coronary angiography who underwent symptom-limited CPET. We assessed ischemic response using predicted % peak VO<sub>2</sub>, O<sub>2</sub> pulse trajectory, and exercise ECG test.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Men with NOCAD had significantly lower predicted % peak VO<sub>2</sub> (62% vs. 73%), higher proportions of flattening pattern (16% vs. 2%), and downward patterns of O<sub>2</sub> pulse trajectory (2% vs. 0%) (<i>p</i> < .0001) compared with women. In contrast, women with NOCAD had a higher prevalence of shallow patterns of O<sub>2</sub> pulse trajectory (21% vs. 6%, <i>p</i> < .0001). Men with NOCAD had a higher risk ischemic profile (medium risk: 63% vs. 54%, high risk: 18% vs. 4%, <i>p</i> < .0001). After adjustment, men with NOCAD had significantly lower predicted % peak VO<sub>2</sub> (β −27.4, 95% CI −30.74 to −24.07), higher risk for abnormal O<sub>2</sub> pulse trajectories (OR 4.21, 95% CI 1.93 to 9.19), and myocardial ischemia risk per CPET parameters (OR 3.14, 95% CI 1.78 to 5.54) (<i>p</i> < .0001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Men with NOCAD had a higher risk profile for ischemic heart disease per CPET. Therefore, they should receive rigorous management and follow-up to prevent cardiovascular events.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139481070","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}
Coronary microvascular dysfunction (CMD) plays a major role in hypertrophic cardiomyopathy (HCM) physiopathology but its assessment in clinical practice remains a challenge. Nowadays, innovations in invasive and noninvasive coronary evaluation using multimodal imaging provide options for the diagnosis of CMD. The objective of the present study was to investigate if new multimodal imaging diagnosis of CMD could detect HCM patients with more impaired cardiac function by left atrioventricular coupling index (LACI).
Methods and Results
A total of 32 consecutive patients with a confirmed diagnosis of HCM (62 ± 13 years, 62% men) were prospectively screened for CMD using a multimodal imaging method. LACI was assessed by cardiovascular magnetic resonance imaging. Fifteen (47%) patients had CMD by multimodal imaging method. Patients with CMD presented a significantly higher LACI (48.5 ± 25.4 vs. 32.5 ± 10.6, p = .03). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LACI (OR = 1.069, 95% CI 1.00–1.135, p = .03).
Conclusion
Multimodal imaging diagnosis of CMD is applicable to HCM patients and is associated with more impaired cardiac function.
{"title":"Coronary microvascular dysfunction as assessed by multimodal diagnostic imaging in patients with hypertrophic cardiomyopathy is related to the severity of cardiac dysfunction","authors":"Tien Vuong Tran, Loic Djaileb, Laurent Riou, Lea Ruez Lantuejoul, Joris Giai, Gilles Barone-Rochette","doi":"10.1111/micc.12843","DOIUrl":"10.1111/micc.12843","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Coronary microvascular dysfunction (CMD) plays a major role in hypertrophic cardiomyopathy (HCM) physiopathology but its assessment in clinical practice remains a challenge. Nowadays, innovations in invasive and noninvasive coronary evaluation using multimodal imaging provide options for the diagnosis of CMD. The objective of the present study was to investigate if new multimodal imaging diagnosis of CMD could detect HCM patients with more impaired cardiac function by left atrioventricular coupling index (LACI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>A total of 32 consecutive patients with a confirmed diagnosis of HCM (62 ± 13 years, 62% men) were prospectively screened for CMD using a multimodal imaging method. LACI was assessed by cardiovascular magnetic resonance imaging. Fifteen (47%) patients had CMD by multimodal imaging method. Patients with CMD presented a significantly higher LACI (48.5 ± 25.4 vs. 32.5 ± 10.6, <i>p</i> = .03). A multivariate logistic regression analysis demonstrated that CMD was independently associated with LACI (OR = 1.069, 95% CI 1.00–1.135, <i>p</i> = .03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Multimodal imaging diagnosis of CMD is applicable to HCM patients and is associated with more impaired cardiac function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139087468","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}
Adina E. Draghici, Matthew R. Ely, Jason W. Hamner, J. Andrew Taylor
Objective
Regulation of blood flow to bone is critical but poorly understood, particularly in humans. This study aims to determine whether nitric oxide (NO), a major regulator of vascular tone to other tissues, contributes also to the regulation of blood flow to bone.
Methods
In young healthy adults (n = 16, 8F, 8M), we characterized NO-mediated vasodilation in the tibia in response to sublingual nitroglycerin and contrasted it to lower leg. Blood flow responses were assessed in supine individuals by continuously measuring tibial total hemoglobin (tHb) via near-infrared spectroscopy and lower leg blood flow (LBF) as popliteal flow velocity via Doppler ultrasound in the same leg.
Results
LBF increased by Δ9.73 ± 0.66 cm/s and peaked 4.4 min after NO administration and declined slowly but remained elevated (Δ3.63 ± 0.60 cm/s) at 10 min. In contrast, time to peak response was longer and smaller in magnitude in the tibia as tHb increased Δ2.08 ± 0.22 μM and peaked 5.3 min after NO administration and declined quickly but remained elevated (Δ0.87±0.22 μM) at 10 min (p = .01).
Conclusions
In young adults, the tibial vasculature demonstrates robust NO-mediated vasodilation, but tHb is delayed and diminishes faster compared to LBF, predominately reflective of skeletal muscle responses. Thus, NO-mediated vasodilation in bone may be characteristically different from other vascular beds.
{"title":"Nitric oxide-mediated vasodilation in human bone","authors":"Adina E. Draghici, Matthew R. Ely, Jason W. Hamner, J. Andrew Taylor","doi":"10.1111/micc.12842","DOIUrl":"10.1111/micc.12842","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Regulation of blood flow to bone is critical but poorly understood, particularly in humans. This study aims to determine whether nitric oxide (NO), a major regulator of vascular tone to other tissues, contributes also to the regulation of blood flow to bone.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In young healthy adults (<i>n</i> = 16, 8F, 8M), we characterized NO-mediated vasodilation in the tibia in response to sublingual nitroglycerin and contrasted it to lower leg. Blood flow responses were assessed in supine individuals by continuously measuring tibial total hemoglobin (tHb) via near-infrared spectroscopy and lower leg blood flow (LBF) as popliteal flow velocity via Doppler ultrasound in the same leg.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>LBF increased by Δ9.73 ± 0.66 cm/s and peaked 4.4 min after NO administration and declined slowly but remained elevated (Δ3.63 ± 0.60 cm/s) at 10 min. In contrast, time to peak response was longer and smaller in magnitude in the tibia as tHb increased Δ2.08 ± 0.22 μM and peaked 5.3 min after NO administration and declined quickly but remained elevated (Δ0.87±0.22 μM) at 10 min (<i>p</i> = .01).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In young adults, the tibial vasculature demonstrates robust NO-mediated vasodilation, but tHb is delayed and diminishes faster compared to LBF, predominately reflective of skeletal muscle responses. Thus, NO-mediated vasodilation in bone may be characteristically different from other vascular beds.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830408","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}
Rafal Gulej, Boglarka Csik, Janet Faakye, Stefano Tarantini, Santny Shanmugarama, Siva Sai Chandragiri, Peter Mukli, Shannon Conley, Anna Csiszar, Zoltan Ungvari, Andriy Yabluchanskiy, Ádám Nyúl-Tóth
Introduction
Age-related blood–brain barrier (BBB) disruption, cerebromicrovascular senescence, and microvascular rarefaction substantially contribute to the pathogenesis of vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Previous studies established a causal link between age-related decline in circulating levels of insulin-like growth factor-1 (IGF-1), cerebromicrovascular dysfunction, and cognitive decline. The aim of our study was to determine the effect of IGF-1 signaling on senescence, BBB permeability, and vascular density in middle-age and old brains.
Methods
Accelerated endothelial senescence was assessed in senescence reporter mice (VE-Cadherin-CreERT2/Igf1rfl/fl × p16-3MR) using flow cytometry. To determine the functional consequences of impaired IGF-1 input to cerebromicrovascular endothelial cells, BBB integrity and capillary density were studied in mice with endothelium-specific knockout of IGF1R (VE-Cadherin-CreERT2/Igf1rfl/fl) using intravital two-photon microscopy.
Results
In VE-Cadherin-CreERT2/Igf1rfl/fl mice: (1) there was an increased presence of senescent endothelial cells; (2) cumulative permeability of the microvessels to fluorescent tracers of different molecular weights (0.3–40 kDa) is significantly increased, as compared to that of control mice, whereas decline in cortical capillary density does not reach statistical significance.
Conclusions
These findings support the notion that IGF-1 signaling plays a crucial role in preserving a youthful cerebromicrovascular endothelial phenotype and maintaining the integrity of the BBB.
{"title":"Endothelial deficiency of insulin-like growth factor-1 receptor leads to blood–brain barrier disruption and accelerated endothelial senescence in mice, mimicking aspects of the brain aging phenotype","authors":"Rafal Gulej, Boglarka Csik, Janet Faakye, Stefano Tarantini, Santny Shanmugarama, Siva Sai Chandragiri, Peter Mukli, Shannon Conley, Anna Csiszar, Zoltan Ungvari, Andriy Yabluchanskiy, Ádám Nyúl-Tóth","doi":"10.1111/micc.12840","DOIUrl":"10.1111/micc.12840","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Age-related blood–brain barrier (BBB) disruption, cerebromicrovascular senescence, and microvascular rarefaction substantially contribute to the pathogenesis of vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Previous studies established a causal link between age-related decline in circulating levels of insulin-like growth factor-1 (IGF-1), cerebromicrovascular dysfunction, and cognitive decline. The aim of our study was to determine the effect of IGF-1 signaling on senescence, BBB permeability, and vascular density in middle-age and old brains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Accelerated endothelial senescence was assessed in senescence reporter mice (<i>VE-Cadherin-Cre</i><sup><i>ERT2</i></sup><i>/Igf1r</i><sup><i>fl/fl</i></sup> × <i>p16-3MR</i>) using flow cytometry. To determine the functional consequences of impaired IGF-1 input to cerebromicrovascular endothelial cells, BBB integrity and capillary density were studied in mice with endothelium-specific knockout of IGF1R (<i>VE-Cadherin-Cre</i><sup><i>ERT2</i></sup><i>/Igf1r</i><sup><i>fl/fl</i></sup>) using intravital two-photon microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In <i>VE-Cadherin-Cre</i><sup><i>ERT2</i></sup><i>/Igf1r</i><sup><i>fl/fl</i></sup> mice: (1) there was an increased presence of senescent endothelial cells; (2) cumulative permeability of the microvessels to fluorescent tracers of different molecular weights (0.3–40 kDa) is significantly increased, as compared to that of control mice, whereas decline in cortical capillary density does not reach statistical significance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings support the notion that IGF-1 signaling plays a crucial role in preserving a youthful cerebromicrovascular endothelial phenotype and maintaining the integrity of the BBB.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138685229","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":"Abstracts from the 48th Annual Meeting of Japanese Society for Microcirculation","authors":"","doi":"10.1111/micc.12836","DOIUrl":"10.1111/micc.12836","url":null,"abstract":"","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138587930","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}
Jacques DuToit, Peter Brothers, Matthew Stephens, Keith Keane, Flavia Neto de Jesus, Simon Roizes, Pierre-Yves von der Weid
Objectives
The objective of our study is to evaluate the involvement of the transient receptor potential vanilloid 4 (TRPV4) in the alteration of lymphatic pumping in response to flow and determine the signaling pathways involved.
Methods
We used immunofluorescence imaging and western blotting to assess TRPV4 expression in rat mesenteric lymphatic vessels. We examined inhibition of TRPV4 with HC067047, nitric oxide synthase (NOS) with L-NNA and cyclooxygenases (COXs) with indomethacin on the contractile response of pressurized lymphatic vessels to flow changes induced by a stepwise increase in pressure gradients, and the functionality of endothelial TRPV4 channels by measuring the intracellular Ca2+ response of primary lymphatic endothelial cell cultures to the selective agonist GSK1016790A.
Results
TRPV4 protein was expressed in both the endothelial and the smooth muscle layer of rat mesenteric lymphatics with high endothelial expression around the valve sites. When maintained under constant transmural pressure, most lymphatic vessels displayed a decrease in contraction frequency under conditions of flow and this effect was ablated through inhibition of NOS, COX or TRPV4.
Conclusions
Our findings demonstrate a critical role for TRPV4 in the decrease in contraction frequency induced in lymphatic vessels by increases in flow rate via the production and action of nitric oxide and dilatory prostanoids.
{"title":"Flow-dependent regulation of rat mesenteric lymphatic vessel contractile response requires activation of endothelial TRPV4 channels","authors":"Jacques DuToit, Peter Brothers, Matthew Stephens, Keith Keane, Flavia Neto de Jesus, Simon Roizes, Pierre-Yves von der Weid","doi":"10.1111/micc.12839","DOIUrl":"10.1111/micc.12839","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The objective of our study is to evaluate the involvement of the transient receptor potential vanilloid 4 (TRPV4) in the alteration of lymphatic pumping in response to flow and determine the signaling pathways involved.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used immunofluorescence imaging and western blotting to assess TRPV4 expression in rat mesenteric lymphatic vessels. We examined inhibition of TRPV4 with HC067047, nitric oxide synthase (NOS) with L-NNA and cyclooxygenases (COXs) with indomethacin on the contractile response of pressurized lymphatic vessels to flow changes induced by a stepwise increase in pressure gradients, and the functionality of endothelial TRPV4 channels by measuring the intracellular Ca<sup>2+</sup> response of primary lymphatic endothelial cell cultures to the selective agonist GSK1016790A.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>TRPV4 protein was expressed in both the endothelial and the smooth muscle layer of rat mesenteric lymphatics with high endothelial expression around the valve sites. When maintained under constant transmural pressure, most lymphatic vessels displayed a decrease in contraction frequency under conditions of flow and this effect was ablated through inhibition of NOS, COX or TRPV4.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings demonstrate a critical role for TRPV4 in the decrease in contraction frequency induced in lymphatic vessels by increases in flow rate via the production and action of nitric oxide and dilatory prostanoids.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478062","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}
Cells have an incredible ability to physically interact with neighboring cells and their environment. They can detect and respond to mechanical forces by converting mechanical stimuli into biochemical signals in a process known as mechanotransduction. This is a key process for the adaption of vascular smooth muscle and endothelial cells to altered flow and pressure conditions. Mechanical stimuli, referring to a physical force exerted on cells, are primarily sensed by transmembrane proteins and the actin cytoskeleton, which initiate a cascade of intracellular events, including the activation of signaling pathways, ion channels, and transcriptional regulators. Recent work has highlighted an important role of the transcriptional coactivators YAP/TAZ for mechanotransduction in vascular cells. Interestingly, the activity of YAP/TAZ decreases with age, providing a potential mechanism for the detrimental effects of aging in the vascular wall. In this review, we summarize the current knowledge on the functional role of YAP and TAZ in vascular endothelial and smooth muscle cells for mechanotransduction in homeostasis and disease. In particular, the review is focused on in vivo observations from conditional knockout (KO) models of YAP/TAZ and the potential implications these studies may have for our understanding of vascular disease development.
{"title":"Emerging role of YAP/TAZ in vascular mechanotransduction and disease","authors":"Olivia Ritsvall, Sebastian Albinsson","doi":"10.1111/micc.12838","DOIUrl":"10.1111/micc.12838","url":null,"abstract":"<p>Cells have an incredible ability to physically interact with neighboring cells and their environment. They can detect and respond to mechanical forces by converting mechanical stimuli into biochemical signals in a process known as mechanotransduction. This is a key process for the adaption of vascular smooth muscle and endothelial cells to altered flow and pressure conditions. Mechanical stimuli, referring to a physical force exerted on cells, are primarily sensed by transmembrane proteins and the actin cytoskeleton, which initiate a cascade of intracellular events, including the activation of signaling pathways, ion channels, and transcriptional regulators. Recent work has highlighted an important role of the transcriptional coactivators YAP/TAZ for mechanotransduction in vascular cells. Interestingly, the activity of YAP/TAZ decreases with age, providing a potential mechanism for the detrimental effects of aging in the vascular wall. In this review, we summarize the current knowledge on the functional role of YAP and TAZ in vascular endothelial and smooth muscle cells for mechanotransduction in homeostasis and disease. In particular, the review is focused on in vivo observations from conditional knockout (KO) models of YAP/TAZ and the potential implications these studies may have for our understanding of vascular disease development.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12838","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138445281","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}
Nadim Naser, Chenchel K. Lonj, Matthew Rikard-Bell, Shaun L. Sandow, Timothy V. Murphy
Objective
This study investigated the actions of advanced glycated end-products (AGE), their receptors (RAGE), and NAD(P)H oxidase (Nox) subtypes 1, 2, and 4 on mechanisms of endothelium-dependent dilation of the rat cremaster muscle artery (CMA).
Methods
Immunofluorescence studies were used to examine expression of RAGE in rat arteries. ROS accumulation was measured using luminescence and fluorescence assays. Functional studies were performed using pressure myography.
Results
High levels of RAGE expression were shown in the endothelial cells of the CMA, compared with low endothelial expression in middle cerebral and mesenteric arteries and the aorta. Exogenous AGE (in vitro glycated bovine serum albumin) stimulated H2O2 accumulation in CMA, which was prevented by the RAGE antagonist FPS-ZM1, the NAD(P)H oxidase (Nox) inhibitor apocynin and inhibited by the Nox1/4 inhibitor setanaxib, but not the Nox2 inhibitor GSK2795039. In functional studies, AGE inhibited vasodilation of CMA stimulated by acetylcholine, sodium nitroprusside, and the BKCa activator NS1619, but not adenosine-induced dilation. FPS-ZM1, apocynin, and setanaxib prevented the inhibitory effects of AGE on responses to acetylcholine and NS-1619.
Conclusion
These observations suggest RAGE are constitutively expressed in the endothelium of the rat CMA and may be activated by AGE to stimulate Nox1/4 and ROS formation with resulting inhibition of NO and BKCa-mediated endothelium-dependent dilation.
{"title":"Advanced glycated end-products inhibit dilation through constitutive endothelial RAGE and Nox1/4 in rat isolated skeletal muscle arteries","authors":"Nadim Naser, Chenchel K. Lonj, Matthew Rikard-Bell, Shaun L. Sandow, Timothy V. Murphy","doi":"10.1111/micc.12837","DOIUrl":"10.1111/micc.12837","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study investigated the actions of advanced glycated end-products (AGE), their receptors (RAGE), and NAD(P)H oxidase (Nox) subtypes 1, 2, and 4 on mechanisms of endothelium-dependent dilation of the rat cremaster muscle artery (CMA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Immunofluorescence studies were used to examine expression of RAGE in rat arteries. ROS accumulation was measured using luminescence and fluorescence assays. Functional studies were performed using pressure myography.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High levels of RAGE expression were shown in the endothelial cells of the CMA, compared with low endothelial expression in middle cerebral and mesenteric arteries and the aorta. Exogenous AGE (in vitro glycated bovine serum albumin) stimulated H2O2 accumulation in CMA, which was prevented by the RAGE antagonist FPS-ZM1, the NAD(P)H oxidase (Nox) inhibitor apocynin and inhibited by the Nox1/4 inhibitor setanaxib, but not the Nox2 inhibitor GSK2795039. In functional studies, AGE inhibited vasodilation of CMA stimulated by acetylcholine, sodium nitroprusside, and the BKCa activator NS1619, but not adenosine-induced dilation. FPS-ZM1, apocynin, and setanaxib prevented the inhibitory effects of AGE on responses to acetylcholine and NS-1619.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These observations suggest RAGE are constitutively expressed in the endothelium of the rat CMA and may be activated by AGE to stimulate Nox1/4 and ROS formation with resulting inhibition of NO and BKCa-mediated endothelium-dependent dilation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"31 1","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12837","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138176586","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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