Joana Costa d'Avila, Aluana Santana Carlos, Raimundo Lima Vieira, Carla Vergueiro, Aline Teixeira Lima, Isaias dos Santos Silva, Vivian Carvalho de Figueiredo, Paulo Henrique Petrone Chateaubriand, Adalgiza Mafra Moreno, Hugo Caire de Castro Faria Neto, Vanessa Estato, Rodrigo Azeredo Siqueira
Objectives
This study aimed to evaluate the effects of the antidiabetics liraglutide, a GLP-1 analog, and empagliflozin, an SGLT-2 inhibitor, on the brain microcirculation of diabetic rats.
Methods
Type 2 diabetes mellitus (DM) was experimentally induced in male Wistar rats by combining a high-fat diet and a low dose of streptozotocin (35 mg/kg). Liraglutide (100 μg/kg s.c.) and empagliflozin (10 mg/kg, oral) were administered for 5 weeks. Body weight was monitored periodically. Oral glucose tolerance, fasting glycemia, and blood triglycerides were evaluated after the treatments. Endothelial–leukocyte interactions in the brain microcirculation and structural capillary density were assessed.
Results
DM rats presented metabolic and cerebrovascular alterations. Liraglutide treatment decreased body weight and blood triglycerides of DM rats. Empagliflozin treatment improved glucose tolerance but only the combination therapy significantly reduced fasting blood glucose. Both treatments and their combination reduced leukocyte adhesion into the endothelium of brain venules. However, empagliflozin was more effective in preventing DM-induced microvascular rarefaction.
Conclusion
These findings suggest that chronic treatment with SGLT2 inhibitors and GLP-1 receptor agonists may serve as potential therapeutic approaches to prevent microvascular complications associated with diabetes.
{"title":"Beneficial effects of empagliflozin and liraglutide on the cerebral microcirculation of diabetic rats","authors":"Joana Costa d'Avila, Aluana Santana Carlos, Raimundo Lima Vieira, Carla Vergueiro, Aline Teixeira Lima, Isaias dos Santos Silva, Vivian Carvalho de Figueiredo, Paulo Henrique Petrone Chateaubriand, Adalgiza Mafra Moreno, Hugo Caire de Castro Faria Neto, Vanessa Estato, Rodrigo Azeredo Siqueira","doi":"10.1111/micc.12825","DOIUrl":"10.1111/micc.12825","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study aimed to evaluate the effects of the antidiabetics liraglutide, a GLP-1 analog, and empagliflozin, an SGLT-2 inhibitor, on the brain microcirculation of diabetic rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Type 2 diabetes mellitus (DM) was experimentally induced in male Wistar rats by combining a high-fat diet and a low dose of streptozotocin (35 mg/kg). Liraglutide (100 μg/kg s.c.) and empagliflozin (10 mg/kg, oral) were administered for 5 weeks. Body weight was monitored periodically. Oral glucose tolerance, fasting glycemia, and blood triglycerides were evaluated after the treatments. Endothelial–leukocyte interactions in the brain microcirculation and structural capillary density were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>DM rats presented metabolic and cerebrovascular alterations. Liraglutide treatment decreased body weight and blood triglycerides of DM rats. Empagliflozin treatment improved glucose tolerance but only the combination therapy significantly reduced fasting blood glucose. Both treatments and their combination reduced leukocyte adhesion into the endothelium of brain venules. However, empagliflozin was more effective in preventing DM-induced microvascular rarefaction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that chronic treatment with SGLT2 inhibitors and GLP-1 receptor agonists may serve as potential therapeutic approaches to prevent microvascular complications associated with diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9953870","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}
ZheHao Tan, Pam Hall, Adam Costin, Simon A. Crawford, Georg Ramm, Connie H. Y. Wong, A. Richard Kitching, Michael J. Hickey
Objective
The endothelial surface layer (ESL), a layer of macromolecules on the surface of endothelial cells, can both impede and facilitate leukocyte recruitment. However, its role in monocyte and neutrophil recruitment in glomerular capillaries is unknown.
Methods
We used multiphoton intravital microscopy to examine monocyte and neutrophil behavior in the glomerulus following ESL disruption with hyaluronidase.
Results
Constitutive retention and migration of monocytes and neutrophils within the glomerular microvasculature was unaltered by hyaluronidase. Consistent with this, inhibition of the hyaluronan-binding molecule CD44 also failed to modulate glomerular trafficking of these immune cells. To investigate the contribution of the ESL during acute inflammation, we induced glomerulonephritis via in situ immune complex deposition. This resulted in increases in glomerular retention of monocytes and neutrophils but did not induce marked reduction in the glomerular ESL. Furthermore, hyaluronidase treatment did not modify the prolonged retention of monocytes and neutrophils in the acutely inflamed glomerular microvasculature.
Conclusions
These observations indicate that, despite evidence that the ESL has the capacity to inhibit leukocyte-endothelial cell interactions while also containing adhesive ligands for immune cells, neither of these functions modulate trafficking of monocytes and neutrophils in steady-state or acutely-inflamed glomeruli.
{"title":"Removal of the endothelial surface layer via hyaluronidase does not modulate monocyte and neutrophil interactions with the glomerular endothelium","authors":"ZheHao Tan, Pam Hall, Adam Costin, Simon A. Crawford, Georg Ramm, Connie H. Y. Wong, A. Richard Kitching, Michael J. Hickey","doi":"10.1111/micc.12823","DOIUrl":"10.1111/micc.12823","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The endothelial surface layer (ESL), a layer of macromolecules on the surface of endothelial cells, can both impede and facilitate leukocyte recruitment. However, its role in monocyte and neutrophil recruitment in glomerular capillaries is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used multiphoton intravital microscopy to examine monocyte and neutrophil behavior in the glomerulus following ESL disruption with hyaluronidase.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Constitutive retention and migration of monocytes and neutrophils within the glomerular microvasculature was unaltered by hyaluronidase. Consistent with this, inhibition of the hyaluronan-binding molecule CD44 also failed to modulate glomerular trafficking of these immune cells. To investigate the contribution of the ESL during acute inflammation, we induced glomerulonephritis via in situ immune complex deposition. This resulted in increases in glomerular retention of monocytes and neutrophils but did not induce marked reduction in the glomerular ESL. Furthermore, hyaluronidase treatment did not modify the prolonged retention of monocytes and neutrophils in the acutely inflamed glomerular microvasculature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These observations indicate that, despite evidence that the ESL has the capacity to inhibit leukocyte-endothelial cell interactions while also containing adhesive ligands for immune cells, neither of these functions modulate trafficking of monocytes and neutrophils in steady-state or acutely-inflamed glomeruli.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234592","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}
Mai Azuma, Shingo Kato, Kazuki Fukui, Nobuyuki Horita, Daisuke Utsunomiya
Background
Although microvascular dysfunction (MVD) is considered an essential pathophysiology in patients with heart failure with preserved ejection fraction (HFpEF), the frequency and prognostic impact of MVD are not fully understood. This meta-analysis evaluated the frequency of MVD in patients with HFpEF and its utility in risk stratification.
Materials and Methods
On May 26, 2022, a literature search was performed on PubMed, Web of Science, the Cochrane library, and Embase using the search terms such as “Heart failure with preserved ejection fraction,” “HFpEF,” “microvascular dysfunction,” and “MVD.” The prevalence of MVD in patients with HFpEF was calculated using the general inverse variance method. A comprehensive literature review was conducted to examine the association between MVD and prognosis in patients with HFpEF.
Results
Data pertaining to a total of 941 patients diagnosed with HFpEF were extracted from the collective pool of 9 studies. The results of the meta-analysis revealed that the frequency of MVD among patients with HFpEF was found to be 55.5% (95% CI: 34.8%–76.2%), with a substantial degree of heterogeneity (I2 = 98%, p for heterogeneity <.001). Among the five studies that provided data on the association between MVD and prognosis, a significant statistical association was observed in four of them.
Conclusions
This meta-analysis revealed that approximately 50% of patients diagnosed with HFpEF exhibited MVD. Moreover, the presence of MVD demonstrated significant prognostic implications in multiple studies conducted on patients with HFpEF. These findings strongly suggest that MVD plays a crucial role in the underlying pathophysiology of patients with HFpEF.
背景：尽管微血管功能障碍（MVD）被认为是射血分数保留（HFpEF）的心力衰竭患者的一种重要病理生理学，但MVD的频率和预后影响尚不完全清楚。这项荟萃分析评估了HFpEF患者MVD的频率及其在风险分层中的作用。材料和方法：2022年5月26日，在PubMed、Web of Science、Cochrane图书馆和Embase上使用“射血分数保留的心力衰竭”、“HFpEF”、“微血管功能障碍”和“MVD”等搜索词进行文献检索。使用通用逆方差法计算HFpEF患者的MVD患病率。对HFpEF患者的MVD与预后之间的关系进行了全面的文献综述。结果：从9项研究的集合中提取了941名诊断为HFpEF的患者的相关数据。荟萃分析结果显示，HFpEF患者的MVD发生率为55.5%（95%CI:34.8%-76.2%），具有显著的异质性（I2 = 98%，异质性为p结论：该荟萃分析显示，约50%的HFpEF患者表现出MVD。此外，在对HFpEF患者进行的多项研究中，MVD的存在显示出显著的预后影响。这些发现有力地表明，MVD在HFpEF患者的潜在病理生理学中起着至关重要的作用。
{"title":"Microvascular dysfunction in patients with heart failure with preserved ejection fraction: A meta-analysis","authors":"Mai Azuma, Shingo Kato, Kazuki Fukui, Nobuyuki Horita, Daisuke Utsunomiya","doi":"10.1111/micc.12822","DOIUrl":"10.1111/micc.12822","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Although microvascular dysfunction (MVD) is considered an essential pathophysiology in patients with heart failure with preserved ejection fraction (HFpEF), the frequency and prognostic impact of MVD are not fully understood. This meta-analysis evaluated the frequency of MVD in patients with HFpEF and its utility in risk stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>On May 26, 2022, a literature search was performed on PubMed, Web of Science, the Cochrane library, and Embase using the search terms such as “Heart failure with preserved ejection fraction,” “HFpEF,” “microvascular dysfunction,” and “MVD.” The prevalence of MVD in patients with HFpEF was calculated using the general inverse variance method. A comprehensive literature review was conducted to examine the association between MVD and prognosis in patients with HFpEF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Data pertaining to a total of 941 patients diagnosed with HFpEF were extracted from the collective pool of 9 studies. The results of the meta-analysis revealed that the frequency of MVD among patients with HFpEF was found to be 55.5% (95% CI: 34.8%–76.2%), with a substantial degree of heterogeneity (<i>I</i><sup>2</sup> = 98%, <i>p</i> for heterogeneity <.001). Among the five studies that provided data on the association between MVD and prognosis, a significant statistical association was observed in four of them.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This meta-analysis revealed that approximately 50% of patients diagnosed with HFpEF exhibited MVD. Moreover, the presence of MVD demonstrated significant prognostic implications in multiple studies conducted on patients with HFpEF. These findings strongly suggest that MVD plays a crucial role in the underlying pathophysiology of patients with HFpEF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9861917","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}
Vibujithan Vigneshwaran, Christine Lauren Sy, Bruce H. Smaill, Gregory B. Sands, Nicolas P. Smith
Recent advances in tissue clearing and high‐throughput imaging have enabled the acquisition of extended‐volume microvasculature images at a submicron resolution. The objective of this study was to extract information from this type of images by integrating a sequence of 3D image processing steps on Terabyte scale datasets.
{"title":"Extended-volume image-derived models of coronary microcirculation","authors":"Vibujithan Vigneshwaran, Christine Lauren Sy, Bruce H. Smaill, Gregory B. Sands, Nicolas P. Smith","doi":"10.1111/micc.12820","DOIUrl":"10.1111/micc.12820","url":null,"abstract":"Recent advances in tissue clearing and high‐throughput imaging have enabled the acquisition of extended‐volume microvasculature images at a submicron resolution. The objective of this study was to extract information from this type of images by integrating a sequence of 3D image processing steps on Terabyte scale datasets.","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 5-6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12820","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10342682","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}
Ryan A. P. Homes, Fiona Giddens, Ross S. Francis, Ruth E. Hubbard, Emily H. Gordon, Mark J. Midwinter
Objective
To examine the relationship between sublingual microcirculatory measures and frailty index in those attending a kidney transplant assessment clinic.
Methods
Patients recruited had their sublingual microcirculation taken using sidestream dark field videomicroscopy (MicroScan, Micro Vision Medical, Amsterdam, the Netherlands) and their frailty index score using a validated short form via interview.
Results
A total of 44 patients were recruited with two being excluded due to microcirculatory image quality scores exceeding 10. The frailty index score indicated significant correlations with total vessel density (p < .0001, r = −.56), microvascular flow index (p = .004, r = −.43), portion of perfused vessels (p = .0004, r = −.52), heterogeneity index (p = .015, r = .32), and perfused vessel density (p < .0001, r = −.66). No correlation was shown between the frailty index and age (p = .08, r = .27).
Conclusions
There is a relationship between the frailty index and microcirculatory health in those attending a kidney transplant assessment clinic, that is not confounded by age. These findings suggest that the impaired microcirculation may be an underlying cause of frailty.
目的探讨肾移植评估门诊患者舌下微循环指标与衰弱指数的关系。方法采用侧流暗场视频显微镜(MicroScan, Micro Vision Medical, Amsterdam, Netherlands)对入选患者进行舌下微循环检查，并采用经验证的短表格进行访谈，对患者进行衰弱指数评分。结果共纳入44例患者，其中2例因微循环图像质量评分超过10分而被排除。衰弱指数评分与总血管密度呈显著相关(p <)。0001, r =−0.56)，微血管流动指数(p = 0.56)。004, r = - 0.43)，灌注血管部分(p =。0004, r =−.52)，异质性指数(p =。015, r = .32)，灌注血管密度(p <0001, r =−0.66)。虚弱指数与年龄无相关性(p =。08, r = .27)。结论肾移植评估门诊患者虚弱指数与微循环健康之间存在相关性，且不受年龄的影响。这些发现表明微循环受损可能是虚弱的潜在原因。
{"title":"The sublingual microcirculation and frailty index in chronic kidney disease patients","authors":"Ryan A. P. Homes, Fiona Giddens, Ross S. Francis, Ruth E. Hubbard, Emily H. Gordon, Mark J. Midwinter","doi":"10.1111/micc.12819","DOIUrl":"10.1111/micc.12819","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To examine the relationship between sublingual microcirculatory measures and frailty index in those attending a kidney transplant assessment clinic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients recruited had their sublingual microcirculation taken using sidestream dark field videomicroscopy (MicroScan, Micro Vision Medical, Amsterdam, the Netherlands) and their frailty index score using a validated short form via interview.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 44 patients were recruited with two being excluded due to microcirculatory image quality scores exceeding 10. The frailty index score indicated significant correlations with total vessel density (<i>p</i> < .0001, <i>r</i> = −.56), microvascular flow index (<i>p</i> = .004, <i>r</i> = −.43), portion of perfused vessels (<i>p</i> = .0004, <i>r</i> = −.52), heterogeneity index (<i>p</i> = .015, <i>r</i> = .32), and perfused vessel density (<i>p</i> < .0001, <i>r</i> = −.66). No correlation was shown between the frailty index and age (<i>p</i> = .08, <i>r</i> = .27).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>There is a relationship between the frailty index and microcirculatory health in those attending a kidney transplant assessment clinic, that is not confounded by age. These findings suggest that the impaired microcirculation may be an underlying cause of frailty.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 5-6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12819","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9985834","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}
Julie Leonard-Duke, Anthony C. Bruce, Shayn M. Peirce, Lakeshia J. Taite
Objective
Microvascular remodeling is governed by biomechanical and biochemical cues which are dysregulated in idiopathic pulmonary fibrosis. Understanding how these cues impact endothelial cell-pericyte interactions necessitates a model system in which both variables can be independently and reproducibly modulated. In this study we develop a tunable hydrogel-based angiogenesis assay to study how varying angiogenic growth factors and environmental stiffness affect sprouting and vessel organization.
Methods
Lungs harvested from mice were cut into 1 mm long segments then cultured on hydrogels having one of seven possible stiffness and growth factor combinations. Time course, brightfield, and immunofluorescence imaging were used to observe and quantify sprout formation.
Results
Our assay was able to support angiogenesis in a comparable manner to Matrigel in soft 2 kPa gels while enabling tunability to study the effects of stiffness on sprout formation. Matrigel and 2 kPa groups contained significantly more samples with sprouts when compared to the stiffer 10 and 20 kPa gels. Growth factor treatment did not have as obvious an effect, although the 20 kPa PDGF + FGF-treated group had significantly longer vessels than the vascular endothelial growth factor-treated group.
Conclusions
We have developed a novel, tunable hydrogel assay for the creation of lung explant vessel organoids which can be modulated to study the impact of specific environmental cues on vessel formation and maturation.
{"title":"Variations in mechanical stiffness alter microvascular sprouting and stability in a PEG hydrogel model of idiopathic pulmonary fibrosis","authors":"Julie Leonard-Duke, Anthony C. Bruce, Shayn M. Peirce, Lakeshia J. Taite","doi":"10.1111/micc.12817","DOIUrl":"10.1111/micc.12817","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Microvascular remodeling is governed by biomechanical and biochemical cues which are dysregulated in idiopathic pulmonary fibrosis. Understanding how these cues impact endothelial cell-pericyte interactions necessitates a model system in which both variables can be independently and reproducibly modulated. In this study we develop a tunable hydrogel-based angiogenesis assay to study how varying angiogenic growth factors and environmental stiffness affect sprouting and vessel organization.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Lungs harvested from mice were cut into 1 mm long segments then cultured on hydrogels having one of seven possible stiffness and growth factor combinations. Time course, brightfield, and immunofluorescence imaging were used to observe and quantify sprout formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our assay was able to support angiogenesis in a comparable manner to Matrigel in soft 2 kPa gels while enabling tunability to study the effects of stiffness on sprout formation. Matrigel and 2 kPa groups contained significantly more samples with sprouts when compared to the stiffer 10 and 20 kPa gels. Growth factor treatment did not have as obvious an effect, although the 20 kPa PDGF + FGF-treated group had significantly longer vessels than the vascular endothelial growth factor-treated group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We have developed a novel, tunable hydrogel assay for the creation of lung explant vessel organoids which can be modulated to study the impact of specific environmental cues on vessel formation and maturation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 5-6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9997375","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}
Alessandro Gentilin, Paolo Moghetti, Antonio Cevese, Anna Vittoria Mattioli, Federico Schena, Cantor Tarperi
Objective
Cardiovascular events show morning preference and sex differences, and are related to aging and type 2 diabetes. We assessed circadian variations and sex differences in vascular conductance (VC) and blood flow (BF) regulations following a brief bout of forearm ischemia.
Methods
Young healthy individuals (H18-30) and elderly without (H50-80) and with type 2 diabetes (T2DM50-80) of both sexes were included. Forearm VC and BF, and mean arterial pressure (MAP) at baseline and following circulatory reperfusion were measured at 6 a.m. and 9 p.m.
Results
In the morning compared to evening, following reperfusion, the VC and BF increments were similar in H18-30 (p>.71), but lower in H50-80 (p<.001) and T2DM50-80 (p<.01). VC and BF following circulatory reperfusion were higher in men than women in H18-30 (p<.001), but similar between sexes in the older groups (p>.23).
Conclusions
Forearm vasodilation following reperfusion is attenuated in the morning in the elderly, impairing BF towards an ischemic area. Diabetes does not affect the circadian regulation of VC and BF, but that of MAP. There are sex differences in VC and BF at baseline and after circulatory reperfusion at a young age, being greater in men, which disappear with aging without being affected by diabetes.
{"title":"Circadian and sex differences in post-ischemic vasodilation and reactive hyperemia in young individuals and elderly with and without type 2 diabetes","authors":"Alessandro Gentilin, Paolo Moghetti, Antonio Cevese, Anna Vittoria Mattioli, Federico Schena, Cantor Tarperi","doi":"10.1111/micc.12818","DOIUrl":"10.1111/micc.12818","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Cardiovascular events show morning preference and sex differences, and are related to aging and type 2 diabetes. We assessed circadian variations and sex differences in vascular conductance (VC) and blood flow (BF) regulations following a brief bout of forearm ischemia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Young healthy individuals (H18-30) and elderly without (H50-80) and with type 2 diabetes (T2DM50-80) of both sexes were included. Forearm VC and BF, and mean arterial pressure (MAP) at baseline and following circulatory reperfusion were measured at 6 a.m. and 9 p.m.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In the morning compared to evening, following reperfusion, the VC and BF increments were similar in H18-30 (p<i>></i>.71), but lower in H50-80 (p<i><</i>.001) and T2DM50-80 (p<i><</i>.01). VC and BF following circulatory reperfusion were higher in men than women in H18-30 (p<i><</i>.001), but similar between sexes in the older groups (p<i>></i>.23).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Forearm vasodilation following reperfusion is attenuated in the morning in the elderly, impairing BF towards an ischemic area. Diabetes does not affect the circadian regulation of VC and BF, but that of MAP. There are sex differences in VC and BF at baseline and after circulatory reperfusion at a young age, being greater in men, which disappear with aging without being affected by diabetes.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 5-6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9970418","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}
William F. Jackson, Armond Daci, Janice M. Thompson, Gregory D. Fink, Stephanie W. Watts
Objective
Serotonin (5-HT) infusion in vivo causes hypotension and a fall in total peripheral resistance. However, the vascular segment and the receptors that mediate this response remain in question. We hypothesized that 5-HT7 receptors mediate arteriolar dilation to 5-HT in skeletal muscle microcirculation.
Methods
Cremaster muscles of isoflurane-anesthetized male Sprague-Dawley rats were prepared for in vivo microscopy of third- and fourth-order arterioles and superfused with physiological salt solution at 34°C. Quantitative real-time PCR (RT-PCR) was applied to pooled samples of first- to third-order cremaster arterioles (2–4 rats/sample) to evaluate 5-HT7 receptor expression.
Results
Topical 5-HT (1–10 nmols) or the 5-HT1/7 receptor agonist, 5-carboxamidotryptamine (10–30 nM), dilated third- and fourth-order arterioles, responses that were abolished by 1 μM SB269970, a selective 5-HT7 receptor antagonist. In contrast, dilation induced by the muscarinic agonist, methacholine (100 nmols) was not inhibited by SB269970. Serotonin (10 nmols) failed to dilate cremaster arterioles in 5-HT7 receptor knockout rats whereas arterioles in wild-type litter mates dilated to 1 nmol 5-HT, a response blocked by 1 μM SB269970. Quantitative RT-PCR revealed that cremaster arterioles expressed mRNA for 5-HT7 receptors.
Conclusions
5-HT7 receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to 5-HT-induced hypotension, in vivo.
{"title":"5-HT7 receptors mediate dilation of rat cremaster muscle arterioles in vivo","authors":"William F. Jackson, Armond Daci, Janice M. Thompson, Gregory D. Fink, Stephanie W. Watts","doi":"10.1111/micc.12808","DOIUrl":"https://doi.org/10.1111/micc.12808","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Serotonin (5-HT) infusion in vivo causes hypotension and a fall in total peripheral resistance. However, the vascular segment and the receptors that mediate this response remain in question. We hypothesized that 5-HT<sub>7</sub> receptors mediate arteriolar dilation to 5-HT in skeletal muscle microcirculation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Cremaster muscles of isoflurane-anesthetized male Sprague-Dawley rats were prepared for in vivo microscopy of third- and fourth-order arterioles and superfused with physiological salt solution at 34°C. Quantitative real-time PCR (RT-PCR) was applied to pooled samples of first- to third-order cremaster arterioles (2–4 rats/sample) to evaluate 5-HT<sub>7</sub> receptor expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Topical 5-HT (1–10 nmols) or the 5-HT<sub>1/7</sub> receptor agonist, 5-carboxamidotryptamine (10–30 nM), dilated third- and fourth-order arterioles, responses that were abolished by 1 μM SB269970, a selective 5-HT<sub>7</sub> receptor antagonist. In contrast, dilation induced by the muscarinic agonist, methacholine (100 nmols) was not inhibited by SB269970. Serotonin (10 nmols) failed to dilate cremaster arterioles in 5-HT<sub>7</sub> receptor knockout rats whereas arterioles in wild-type litter mates dilated to 1 nmol 5-HT, a response blocked by 1 μM SB269970. Quantitative RT-PCR revealed that cremaster arterioles expressed mRNA for 5-HT<sub>7</sub> receptors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>5-HT<sub>7</sub> receptors mediate dilation of small arterioles in skeletal muscle and likely contribute to 5-HT-induced hypotension, in vivo.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 5-6","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12808","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50137922","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}
Zulkefli Sanip, Nurnajwa Pahimi, Nur Adilah Bokti, Zurkurnai Yusof, Mohd Sapawi Mohamed, W. Yus Haniff W. Isa, Aida Hanum Rasool
Objective
This study aimed to determine whether peripheral microvascular reactivity is impaired in patients with nonobstructive coronary artery disease (NOCAD).
Methods
Stable patients presenting with angina were recruited and, based on results from coronary angiography, were categorized into OCAD (coronary stenosis of ≥50%) and NOCAD (stenosis <50%) groups. A control group with no history of angina was also recruited. Forearm skin microvascular reactivity was measured using the laser Doppler blood perfusion monitor and the process of postocclusive skin reactive hyperemia (PORH).
Results
Patients were categorized into OCAD (n = 42), NOCAD (n = 40), and control (n = 39) groups. Compared with the control group, the PORH perfusion percent change (PORH% change) was significantly lower in the OCAD and NOCAD groups. No significant differences were noted between the OCAD and NOCAD groups. Additionally, the NOCAD group without any coronary obstruction takes a longer time to reach peak perfusion and had lower PORH% change compared with the nonangina control group.
Conclusion
Angina patients with NOCAD have microvascular dysfunction as demonstrated by reduced magnitude of reperfusion with an ischemic stimulus. NOCAD patients without coronary obstruction also displayed a slower response to reperfusion.
{"title":"Impaired peripheral microvascular reactivity in patients with nonobstructive coronary artery disease","authors":"Zulkefli Sanip, Nurnajwa Pahimi, Nur Adilah Bokti, Zurkurnai Yusof, Mohd Sapawi Mohamed, W. Yus Haniff W. Isa, Aida Hanum Rasool","doi":"10.1111/micc.12807","DOIUrl":"10.1111/micc.12807","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This study aimed to determine whether peripheral microvascular reactivity is impaired in patients with nonobstructive coronary artery disease (NOCAD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Stable patients presenting with angina were recruited and, based on results from coronary angiography, were categorized into OCAD (coronary stenosis of ≥50%) and NOCAD (stenosis <50%) groups. A control group with no history of angina was also recruited. Forearm skin microvascular reactivity was measured using the laser Doppler blood perfusion monitor and the process of postocclusive skin reactive hyperemia (PORH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Patients were categorized into OCAD (<i>n</i> = 42), NOCAD (<i>n</i> = 40), and control (<i>n</i> = 39) groups. Compared with the control group, the PORH perfusion percent change (PORH% change) was significantly lower in the OCAD and NOCAD groups. No significant differences were noted between the OCAD and NOCAD groups. Additionally, the NOCAD group without any coronary obstruction takes a longer time to reach peak perfusion and had lower PORH% change compared with the nonangina control group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Angina patients with NOCAD have microvascular dysfunction as demonstrated by reduced magnitude of reperfusion with an ischemic stimulus. NOCAD patients without coronary obstruction also displayed a slower response to reperfusion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9511850","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}
Sanjukta Chakraborty, Brandon J. Dixon, Joseph M. Rutkowski, Jorge A. Castorena-Gonzalez, Jerome W. Breslin
Lymphatic research has rapidly accelerated and evolved over the last few decades with more clinicians and basic scientists appreciating the huge impact of this vasculature.1 The lymphatic system, with its network of vessels and interconnected nodes, returns interstitial fluid to the blood circulation and is central in the maintenance of fluid homeostasis, immune surveillance, and uptake of dietary lipids.2,3 The development of cuttingedge genetic models and imaging tools to manipulate and visualize lymphatic vessels, coupled with bioengineering approaches applied to the fundamental physiology of lymphatic vessel function, has significantly impacted our current understanding of the critical roles played by lymphatics both during development and in pathophysiological conditions across a plethora of disease states. This Special Topic Issue showcases a collection of primary research and review articles that highlight the diverse roles of lymphatics in disease pathogenesis that could potentially be leveraged to develop novel targeted approaches for therapeutic interventions. The primary research articles in the issue take various approaches to manipulate or target lymphatic vessel growth and function in disease. For example, the study by Michalaki et al.4 describes the therapeutic potential of engineered human mesenchymal stem cells overexpressing vascular endothelial growth factor C (VEGFC), as an autologous cellbased therapeutic treatment, for alleviation of lymphatic dysfunction associated with secondary injury mediated lymphedema. The study by Mahamud et al.5 shows that transcription factor GATA2 promotes blood/lymph separation through platelets and that while lymphovenous valves are the only known sites of interaction between blood and lymphatic vessels, more unidentified sites of interaction possibly exist between blood and lymphatic vessels. Steinskog et al.6 used a rat model mimicking acute myeloid leukemia (AML) with cannulation of efferent lymphatic vessels from the spleen and liver and subsequent proteomic profiling. Their findings revealed a differential response in AMLcell infiltrated spleen and liver, indicating that interstitial fluid and efferent lymph can provide unique information about the specific microenvironment responses that are variable in target organs during AML progression. In the work by Jo et al.,7 the effects of five different components which comprise Goreisan, a traditional herbal formulation (used as a therapeutic in Japan to alleviate lymphedema symptoms), were investigated for their effects on mesenteric lymphatic pumping in rats. They showed that that acute exposure of two components of Goreisan decreased lymphatic pumping in isolated rat mesenteric collecting lymphatics while oral administration of Goreisan induced vascular endothelial growth factor receptor 3 (VEGFR3), in these lymphatic vessels. Jablon et al.8 describe the development of an innovative technique for routine isolation, culture and characterization
{"title":"Lymphatic Pathophysiology","authors":"Sanjukta Chakraborty, Brandon J. Dixon, Joseph M. Rutkowski, Jorge A. Castorena-Gonzalez, Jerome W. Breslin","doi":"10.1111/micc.12806","DOIUrl":"10.1111/micc.12806","url":null,"abstract":"Lymphatic research has rapidly accelerated and evolved over the last few decades with more clinicians and basic scientists appreciating the huge impact of this vasculature.1 The lymphatic system, with its network of vessels and interconnected nodes, returns interstitial fluid to the blood circulation and is central in the maintenance of fluid homeostasis, immune surveillance, and uptake of dietary lipids.2,3 The development of cuttingedge genetic models and imaging tools to manipulate and visualize lymphatic vessels, coupled with bioengineering approaches applied to the fundamental physiology of lymphatic vessel function, has significantly impacted our current understanding of the critical roles played by lymphatics both during development and in pathophysiological conditions across a plethora of disease states. This Special Topic Issue showcases a collection of primary research and review articles that highlight the diverse roles of lymphatics in disease pathogenesis that could potentially be leveraged to develop novel targeted approaches for therapeutic interventions. The primary research articles in the issue take various approaches to manipulate or target lymphatic vessel growth and function in disease. For example, the study by Michalaki et al.4 describes the therapeutic potential of engineered human mesenchymal stem cells overexpressing vascular endothelial growth factor C (VEGFC), as an autologous cellbased therapeutic treatment, for alleviation of lymphatic dysfunction associated with secondary injury mediated lymphedema. The study by Mahamud et al.5 shows that transcription factor GATA2 promotes blood/lymph separation through platelets and that while lymphovenous valves are the only known sites of interaction between blood and lymphatic vessels, more unidentified sites of interaction possibly exist between blood and lymphatic vessels. Steinskog et al.6 used a rat model mimicking acute myeloid leukemia (AML) with cannulation of efferent lymphatic vessels from the spleen and liver and subsequent proteomic profiling. Their findings revealed a differential response in AMLcell infiltrated spleen and liver, indicating that interstitial fluid and efferent lymph can provide unique information about the specific microenvironment responses that are variable in target organs during AML progression. In the work by Jo et al.,7 the effects of five different components which comprise Goreisan, a traditional herbal formulation (used as a therapeutic in Japan to alleviate lymphedema symptoms), were investigated for their effects on mesenteric lymphatic pumping in rats. They showed that that acute exposure of two components of Goreisan decreased lymphatic pumping in isolated rat mesenteric collecting lymphatics while oral administration of Goreisan induced vascular endothelial growth factor receptor 3 (VEGFR3), in these lymphatic vessels. Jablon et al.8 describe the development of an innovative technique for routine isolation, culture and characterization","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2023-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9442087","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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