Kelli L. Jablon, Victoria L. Akerstrom, Min Li, Stephen E. Braun, Charles E. Norton, Jorge A. Castorena-Gonzalez
Objective
To develop an experimental method for routine isolation and short-term culture of primary lymphatic endothelial cells from specific collecting vessels.
Methods
Lymphatic endothelial cell tubes (LECTs) were isolated from micro-dissected collecting vessels. LECTs were allowed to attach and grow for ~3 weeks before being passaged. Non-purified cultures were partially characterized by immunofluorescence and RT-PCR at passages 1–2.
Results
The method was validated in cultures of primary lymphatic endothelial cells (LECs) from male and female mice. After 1 or 2 passages, >60% of the LECs maintained expression of Prox1. Expression of 22 different genes was assessed using RT-PCR. Prox1, Vegfr3, eNos, Cdh5, Pecam1, Cx43, Cx37, and Cx47, among others, were expressed in these short-term cultured LECs, while Myh11, Cnn1, Desmin, and Cd11b were not detected. Prox1 expression, as determined by western blotting, was similar in cultured LECs from age-matched male and female mice. Confocal imaging of intracellular calcium in cultures of primary LECs from Cdh5-GCaMP8 mice demonstrated that a functional phenotype was maintained, similar to lymphatic endothelial cells in freshly isolated vessels.
Conclusions
This method provides an innovative tool for routine isolation and study of primary LECs from specific collecting lymphatic vessels from any mouse, and in fact, from other species.
{"title":"Isolation and short-term culturing of primary lymphatic endothelial cells from collecting lymphatics: A techniques study","authors":"Kelli L. Jablon, Victoria L. Akerstrom, Min Li, Stephen E. Braun, Charles E. Norton, Jorge A. Castorena-Gonzalez","doi":"10.1111/micc.12778","DOIUrl":"10.1111/micc.12778","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To develop an experimental method for routine isolation and short-term culture of primary lymphatic endothelial cells from specific collecting vessels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Lymphatic endothelial cell tubes (LECTs) were isolated from micro-dissected collecting vessels. LECTs were allowed to attach and grow for ~3 weeks before being passaged. Non-purified cultures were partially characterized by immunofluorescence and RT-PCR at passages 1–2.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The method was validated in cultures of primary lymphatic endothelial cells (LECs) from male and female mice. After 1 or 2 passages, >60% of the LECs maintained expression of Prox1. Expression of 22 different genes was assessed using RT-PCR. Prox1, Vegfr3, eNos, Cdh5, Pecam1, Cx43, Cx37, and Cx47, among others, were expressed in these short-term cultured LECs, while Myh11, Cnn1, Desmin, and Cd11b were not detected. Prox1 expression, as determined by western blotting, was similar in cultured LECs from age-matched male and female mice. Confocal imaging of intracellular calcium in cultures of primary LECs from Cdh5-GCaMP8 mice demonstrated that a functional phenotype was maintained, similar to lymphatic endothelial cells in freshly isolated vessels.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This method provides an innovative tool for routine isolation and study of primary LECs from specific collecting lymphatic vessels from any mouse, and in fact, from other species.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/micc.12778","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10111338","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}
Liana Valeanu, Stefan Andrei, Carmen Ginghina, Cornel Robu, Adrian Ciurciun, Cosmin Balan, Mihai Stefan, Anca Stoian, Iulia Stanculea, Andreea Cheta, Laura Dima, Ovidiu Stiru, Daniela Filipescu, Serban-Ion Bubenek-Turconi, Dan Longrois
Objective
Plasma viscosity is one of the critical factors that regulate microcirculatory flow but has received scant research attention. The main objective of this study was to evaluate plasma viscosity in cardiac surgery with respect to perioperative trajectory, main determinants, and impact on outcome.
Methods
Prospective, single center, observational study, including 50 adult patients undergoing cardiac surgery with cardiopulmonary bypass between February 1, 2020 and May 31, 2021. Clinical perioperative characteristics, short term outcome, standard blood analysis, plasma viscosity, total proteins, and fibrinogen concentrations were recorded at 10 distinct time points during the first perioperative week.
Results
The longitudinal analysis showed that plasma viscosity is strongly influenced by proteins and measurement time points. Plasma viscosity showed a coefficient of variation of 11.3 ± 1.08 for EDTA and 12.1 ± 2.1 for citrate, similarly to total proteins and hemoglobin, but significantly lower than fibrinogen (p < .001). Plasma viscosity had lower percentage changes compared to hemoglobin (RANOVA, p < .001), fibrinogen (RANOVA, p < .001), and total proteins (RANOVA, p < .001). The main determinant of plasma viscosity was protein concentrations. No association with outcome was found, but the study may have been underpowered to detect it.
Conclusion
Plasma viscosity had a low coefficient of variation and low perioperative changes, suggesting tight regulation. Studies linking plasma viscosity with outcome would require large patient cohorts.
目的血浆黏度是调节微循环血流的关键因素之一，但目前研究较少。本研究的主要目的是评估心脏手术中血浆粘度与围手术期轨迹、主要决定因素和对结果的影响。方法前瞻性、单中心、观察性研究，纳入2020年2月1日至2021年5月31日期间接受心脏手术合并体外循环的50例成年患者。在围手术期第一周的10个不同时间点记录临床围手术期特征、短期预后、标准血分析、血浆粘度、总蛋白和纤维蛋白原浓度。结果纵向分析表明，血浆粘度受蛋白质和测量时间点的影响较大。血浆粘度变化系数显示EDTA为11.3±1.08，柠檬酸盐为12.1±2.1，与总蛋白和血红蛋白相似，但显著低于纤维蛋白原(p < .001)。与血红蛋白(RANOVA, p < 0.001)、纤维蛋白原(RANOVA, p < 0.001)和总蛋白(RANOVA, p < 0.001)相比，血浆粘度的变化百分比较低。血浆粘度的主要决定因素是蛋白质浓度。没有发现与结果的联系，但这项研究可能没有足够的能力来检测它。结论血浆粘度变化系数小，围手术期变化小，有严密的调控。将血浆粘度与结果联系起来的研究需要大量的患者队列。
{"title":"Perioperative trajectory of plasma viscosity: A prospective, observational, exploratory study in cardiac surgery","authors":"Liana Valeanu, Stefan Andrei, Carmen Ginghina, Cornel Robu, Adrian Ciurciun, Cosmin Balan, Mihai Stefan, Anca Stoian, Iulia Stanculea, Andreea Cheta, Laura Dima, Ovidiu Stiru, Daniela Filipescu, Serban-Ion Bubenek-Turconi, Dan Longrois","doi":"10.1111/micc.12777","DOIUrl":"10.1111/micc.12777","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Plasma viscosity is one of the critical factors that regulate microcirculatory flow but has received scant research attention. The main objective of this study was to evaluate plasma viscosity in cardiac surgery with respect to perioperative trajectory, main determinants, and impact on outcome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Prospective, single center, observational study, including 50 adult patients undergoing cardiac surgery with cardiopulmonary bypass between February 1, 2020 and May 31, 2021. Clinical perioperative characteristics, short term outcome, standard blood analysis, plasma viscosity, total proteins, and fibrinogen concentrations were recorded at 10 distinct time points during the first perioperative week.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The longitudinal analysis showed that plasma viscosity is strongly influenced by proteins and measurement time points. Plasma viscosity showed a coefficient of variation of 11.3 ± 1.08 for EDTA and 12.1 ± 2.1 for citrate, similarly to total proteins and hemoglobin, but significantly lower than fibrinogen (<i>p</i> < .001). Plasma viscosity had lower percentage changes compared to hemoglobin (RANOVA, <i>p</i> < .001), fibrinogen (RANOVA, <i>p</i> < .001), and total proteins (RANOVA, <i>p</i> < .001). The main determinant of plasma viscosity was protein concentrations. No association with outcome was found, but the study may have been underpowered to detect it.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Plasma viscosity had a low coefficient of variation and low perioperative changes, suggesting tight regulation. Studies linking plasma viscosity with outcome would require large patient cohorts.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 4-5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40524878","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}
Shubham Mirg, Kevin L. Turner, Haoyang Chen, Patrick J. Drew, Sri-Rajasekhar Kothapalli
Microcirculation facilitates the blood-tissue exchange of nutrients and regulates blood perfusion. It is, therefore, essential in maintaining tissue health. Aberrations in microcirculation are potentially indicative of underlying cardiovascular and metabolic pathologies. Thus, quantitative information about it is of great clinical relevance. Photoacoustic imaging (PAI) is a capable technique that relies on the generation of imaging contrast via the absorption of light and can image at micron-scale resolution. PAI is especially desirable to map microvasculature as hemoglobin strongly absorbs light and can generate a photoacoustic signal. This paper reviews the current state of the art for imaging microvascular networks using photoacoustic imaging. We further describe how quantitative information about blood dynamics such as the total hemoglobin concentration, oxygen saturation, and blood flow rate is obtained using PAI. We also discuss its importance in understanding key pathophysiological processes in neurovascular, cardiovascular, ophthalmic, and cancer research fields. We then discuss the current challenges and limitations of PAI and the approaches that can help overcome these limitations. Finally, we provide the reader with an overview of future trends in the field of PAI for imaging microcirculation.
{"title":"Photoacoustic imaging for microcirculation","authors":"Shubham Mirg, Kevin L. Turner, Haoyang Chen, Patrick J. Drew, Sri-Rajasekhar Kothapalli","doi":"10.1111/micc.12776","DOIUrl":"10.1111/micc.12776","url":null,"abstract":"<p>Microcirculation facilitates the blood-tissue exchange of nutrients and regulates blood perfusion. It is, therefore, essential in maintaining tissue health. Aberrations in microcirculation are potentially indicative of underlying cardiovascular and metabolic pathologies. Thus, quantitative information about it is of great clinical relevance. Photoacoustic imaging (PAI) is a capable technique that relies on the generation of imaging contrast via the absorption of light and can image at micron-scale resolution. PAI is especially desirable to map microvasculature as hemoglobin strongly absorbs light and can generate a photoacoustic signal. This paper reviews the current state of the art for imaging microvascular networks using photoacoustic imaging. We further describe how quantitative information about blood dynamics such as the total hemoglobin concentration, oxygen saturation, and blood flow rate is obtained using PAI. We also discuss its importance in understanding key pathophysiological processes in neurovascular, cardiovascular, ophthalmic, and cancer research fields. We then discuss the current challenges and limitations of PAI and the approaches that can help overcome these limitations. Finally, we provide the reader with an overview of future trends in the field of PAI for imaging microcirculation.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 6-7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9161040","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}
Hongjiang Si, Chunhiu Yin, Wei Wang, Peter Davies, Elda Sanchez, Montamas Suntravat, David Zawieja, Walter Cromer
Objective
The pathology of snake envenomation is closely tied to the severity of edema in the tissue surrounding the area of the bite. Elucidating the mechanisms that promote the development of such severe edema is critical to a better understanding of how to treat this life-threatening injury. We focused on one of the most abundant venom components in North American viper venom, crotamine, and the effects it has on the cells and function of the lymphatic system.
Methods
We used RT-PCR to identify the location and relative abundance of crotamine's cellular targets (Kvα channels) within the tissues and cells of the lymphatic system. We used calcium flux, nitrate production, and cell morphometry to determine the effects of crotamine on lymphatic endothelial cells. We used tracer transport, node morphometry, and node deposition to determine the effects of crotamine on lymph transport in vivo.
Results
We found that genes that encode targets of crotamine are highly present in lymphatic tissues and cells and that there is a differential distribution of those genes that correlates with phasic contractile activity. We found that crotamine potentiates calcium flux in human dermal lymphatic endothelial cells in response to stimulation with histamine and sheer stress (but not alone) and that it alters the production of nitric oxide in response to shear as well as changes the level of F-actin polymerization of those same cells. Crotamine alters lymphatic transport of large molecular weight tracers to local lymph nodes and is deposited within the node mostly in the immediate subcapsular region.
Conclusion
This evidence suggests that snake venom components may have an impact on the function of the lymphatic system. This needs to be studied in greater detail as there are numerous venom components that may have effects on aspects of the lymphatic system. This would not only provide basic information on the pathobiology of snakebite but also provide targets for improved therapeutics to treat snakebite.
{"title":"Effect of the snake venom component crotamine on lymphatic endothelial cell responses and lymph transport","authors":"Hongjiang Si, Chunhiu Yin, Wei Wang, Peter Davies, Elda Sanchez, Montamas Suntravat, David Zawieja, Walter Cromer","doi":"10.1111/micc.12775","DOIUrl":"10.1111/micc.12775","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>The pathology of snake envenomation is closely tied to the severity of edema in the tissue surrounding the area of the bite. Elucidating the mechanisms that promote the development of such severe edema is critical to a better understanding of how to treat this life-threatening injury. We focused on one of the most abundant venom components in North American viper venom, crotamine, and the effects it has on the cells and function of the lymphatic system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We used RT-PCR to identify the location and relative abundance of crotamine's cellular targets (Kvα channels) within the tissues and cells of the lymphatic system. We used calcium flux, nitrate production, and cell morphometry to determine the effects of crotamine on lymphatic endothelial cells. We used tracer transport, node morphometry, and node deposition to determine the effects of crotamine on lymph transport in vivo.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that genes that encode targets of crotamine are highly present in lymphatic tissues and cells and that there is a differential distribution of those genes that correlates with phasic contractile activity. We found that crotamine potentiates calcium flux in human dermal lymphatic endothelial cells in response to stimulation with histamine and sheer stress (but not alone) and that it alters the production of nitric oxide in response to shear as well as changes the level of F-actin polymerization of those same cells. Crotamine alters lymphatic transport of large molecular weight tracers to local lymph nodes and is deposited within the node mostly in the immediate subcapsular region.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This evidence suggests that snake venom components may have an impact on the function of the lymphatic system. This needs to be studied in greater detail as there are numerous venom components that may have effects on aspects of the lymphatic system. This would not only provide basic information on the pathobiology of snakebite but also provide targets for improved therapeutics to treat snakebite.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9850291/pdf/nihms-1858558.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9656122","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}
Emily E. Morin, Sophia Salbato, Benjimen R. Walker, Jay S. Naik
Objective
Our previous work demonstrated that endothelial cell (EC) membrane cholesterol is reduced following 48 h of chronic hypoxia (CH). CH couples endothelial transient receptor potential subfamily V member 4 (TRPV4) channels to muscarinic receptor signaling through an endothelium-dependent hyperpolarization (EDH) pathway does not present in control animals. TRVPV4 channel activity has been shown to be regulated by membrane cholesterol. Hence, we hypothesize that acute manipulation of endothelial cell membrane cholesterol inversely determines the contribution of TRPV4 channels to endothelium-dependent vasodilation.
Methods
Male Sprague–Dawley rats were exposed to ambient atmospheric (atm.) pressure or 48-h of hypoxia (0.5 atm). Vasodilation to acetylcholine (ACh) was determined using pressure myography in gracilis arteries. EC membrane cholesterol was depleted using methyl-β-cyclodextrin (MβCD) and supplemented with MβCD-cholesterol.
Results
Inhibiting TRPV4 did not affect ACh-induced vasodilation in normoxic controls. However, TRPV4 inhibition reduced resting diameter in control arteries suggesting basal activity. TRPV4 contributes to ACh-induced vasodilation in these arteries when EC membrane cholesterol is depleted. Inhibiting TRPV4 attenuated ACh-induced vasodilation in arteries from CH animals that exhibit lower EC membrane cholesterol than normoxic controls. EC cholesterol repletion in arteries from CH animals abolished the contribution of TRPV4 to ACh-induced vasodilation.
Conclusion
Endothelial cell membrane cholesterol impedes the contribution of TRPV4 channels in EDH-mediated dilation. These results provide additional evidence for the importance of plasma membrane cholesterol content in regulating intracellular signaling and vascular function.
目的我们之前的研究表明，慢性缺氧(CH) 48小时后内皮细胞(EC)膜胆固醇降低。CH偶联内皮瞬时受体电位亚家族V成员4 (TRPV4)通道通过内皮依赖性超极化(EDH)途径传递毒毒碱受体信号，在对照动物中不存在。TRVPV4通道活性已被证明受膜胆固醇调节。因此，我们假设内皮细胞膜胆固醇的急性操纵与TRPV4通道对内皮依赖性血管舒张的贡献相反。方法雄性Sprague-Dawley大鼠暴露于环境大气压(atm)或缺氧48 h (0.5 atm)。用压力肌图测定股薄肌动脉对乙酰胆碱(ACh)的血管舒张。用甲基β-环糊精(m -β- cd)去除EC膜胆固醇，并添加m -β cd -胆固醇。结果抑制TRPV4对乙酰胆碱所致的血管舒张无影响。然而，TRPV4抑制降低了对照动脉的静息直径，提示基础活性。当EC膜胆固醇耗尽时，TRPV4有助于乙酰胆碱诱导的这些动脉血管舒张。抑制TRPV4可减弱乙酰胆碱诱导的动脉血管舒张，这些动物的EC膜胆固醇低于正常氧合对照组。CH动物动脉中EC胆固醇的补充消除了TRPV4对乙酰胆碱诱导的血管舒张的作用。结论内皮细胞膜胆固醇阻碍了TRPV4通道在edh介导的扩张中的作用。这些结果为质膜胆固醇含量在调节细胞内信号和血管功能中的重要性提供了额外的证据。
{"title":"Endothelial cell membrane cholesterol content regulates the contribution of TRPV4 channels in ACh-induced vasodilation in rat gracilis arteries","authors":"Emily E. Morin, Sophia Salbato, Benjimen R. Walker, Jay S. Naik","doi":"10.1111/micc.12774","DOIUrl":"10.1111/micc.12774","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Our previous work demonstrated that endothelial cell (EC) membrane cholesterol is reduced following 48 h of chronic hypoxia (CH). CH couples endothelial transient receptor potential subfamily V member 4 (TRPV4) channels to muscarinic receptor signaling through an endothelium-dependent hyperpolarization (EDH) pathway does not present in control animals. TRVPV4 channel activity has been shown to be regulated by membrane cholesterol. Hence, we hypothesize that acute manipulation of endothelial cell membrane cholesterol inversely determines the contribution of TRPV4 channels to endothelium-dependent vasodilation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Male Sprague–Dawley rats were exposed to ambient atmospheric (atm.) pressure or 48-h of hypoxia (0.5 atm). Vasodilation to acetylcholine (ACh) was determined using pressure myography in gracilis arteries. EC membrane cholesterol was depleted using methyl-β-cyclodextrin (MβCD) and supplemented with MβCD-cholesterol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Inhibiting TRPV4 did not affect ACh-induced vasodilation in normoxic controls. However, TRPV4 inhibition reduced resting diameter in control arteries suggesting basal activity. TRPV4 contributes to ACh-induced vasodilation in these arteries when EC membrane cholesterol is depleted. Inhibiting TRPV4 attenuated ACh-induced vasodilation in arteries from CH animals that exhibit lower EC membrane cholesterol than normoxic controls. EC cholesterol repletion in arteries from CH animals abolished the contribution of TRPV4 to ACh-induced vasodilation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Endothelial cell membrane cholesterol impedes the contribution of TRPV4 channels in EDH-mediated dilation. These results provide additional evidence for the importance of plasma membrane cholesterol content in regulating intracellular signaling and vascular function.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 4-5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10321491","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}
Bjorn Kaijun Betzler, Charumathi Sabanayagam, Yih-Chung Tham, Carol Y. Cheung, Ching-Yu Cheng, Tien-Yin Wong, Simon Nusinovici
Objective
To determine the longitudinal associations between retinal vascular profile (RVP) and four major cardiometabolic diseases; and to quantify the predictive improvements when adding RVP beyond traditional risk factors in individuals with diabetes.
Methods
Subjects were enrolled from the Singapore Epidemiology of Eye Disease (SEED) study, a multi-ethnic population-based cohort. Four incident cardiometabolic diseases, calculated over a ~ 6-year period, were considered: cardiovascular disease (CVD), hypertension (HTN), diabetic kidney disease (DKD), and hyperlipidemia (HLD). The RVP—vessel tortuosity, branching angle, branching coefficient, fractal dimension, vessel caliber, and DR status—was characterized at baseline using a computer-assisted program. Traditional risk factors at baseline included age, gender, ethnicity, smoking, blood pressure (BP), HbA1c, estimated glomerular filtration rate (eGFR), or cholesterol. The improvements in predictive performance when adding RVP (compared with only traditional risk factors) was calculated using several metrics including area under the receiver operating characteristics curve (AUC) and net reclassification improvement (NRI).
Results
Among 1770 individuals with diabetes, incidences were 6.3% (n = 79/1259) for CVD, 48.7% (n = 166/341) for HTN, 14.6% (n = 175/1199) for DKD, and 59.4% (n = 336/566) for HLD. DR preceded the onset of CVD (RR 1.85[1.14;3.00]) and DKD (1.44 [1.06;1.96]). Narrower arteriolar caliber preceding the onset of HTN (0.84 [0.72;0.99]), and changes in arteriolar branching angle preceded the onset of CVD (0.78 [0.62;0.98]) and HTN (1.15 [1.03;1.29]). The largest predictive improvement was found for HTN with AUC increment of 3.4% (p = .027) and better reclassification of 11.4% of the cases and 4.6% of the controls (p = .008).
Conclusion
We found that RVPs improved the prediction of HTN in individuals with diabetes, but add limited information for CVD, DKD, and HLD predictions.
{"title":"Retinal vascular profile in predicting incident cardiometabolic diseases among individuals with diabetes","authors":"Bjorn Kaijun Betzler, Charumathi Sabanayagam, Yih-Chung Tham, Carol Y. Cheung, Ching-Yu Cheng, Tien-Yin Wong, Simon Nusinovici","doi":"10.1111/micc.12772","DOIUrl":"10.1111/micc.12772","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To determine the longitudinal associations between retinal vascular profile (RVP) and four major cardiometabolic diseases; and to quantify the predictive improvements when adding RVP beyond traditional risk factors in individuals with diabetes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Subjects were enrolled from the Singapore Epidemiology of Eye Disease (SEED) study, a multi-ethnic population-based cohort. Four incident cardiometabolic diseases, calculated over a ~ 6-year period, were considered: cardiovascular disease (CVD), hypertension (HTN), diabetic kidney disease (DKD), and hyperlipidemia (HLD). The RVP—vessel tortuosity, branching angle, branching coefficient, fractal dimension, vessel caliber, and DR status—was characterized at baseline using a computer-assisted program. Traditional risk factors at baseline included age, gender, ethnicity, smoking, blood pressure (BP), HbA1c, estimated glomerular filtration rate (eGFR), or cholesterol. The improvements in predictive performance when adding RVP (compared with only traditional risk factors) was calculated using several metrics including area under the receiver operating characteristics curve (AUC) and net reclassification improvement (NRI).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 1770 individuals with diabetes, incidences were 6.3% (<i>n</i> = 79/1259) for CVD, 48.7% (<i>n</i> = 166/341) for HTN, 14.6% (<i>n</i> = 175/1199) for DKD, and 59.4% (<i>n</i> = 336/566) for HLD. DR preceded the onset of CVD (RR 1.85[1.14;3.00]) and DKD (1.44 [1.06;1.96]). Narrower arteriolar caliber preceding the onset of HTN (0.84 [0.72;0.99]), and changes in arteriolar branching angle preceded the onset of CVD (0.78 [0.62;0.98]) and HTN (1.15 [1.03;1.29]). The largest predictive improvement was found for HTN with AUC increment of 3.4% (<i>p</i> = .027) and better reclassification of 11.4% of the cases and 4.6% of the controls (<i>p</i> = .008).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We found that RVPs improved the prediction of HTN in individuals with diabetes, but add limited information for CVD, DKD, and HLD predictions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 4-5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42758678","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}
Ioanna Papagiouvanni, Marieta P. Theodorakopoulou, Pantelis A. Sarafidis, Emmanouil Sinakos, Ioannis Goulis
Objective
This is the first systematic review and meta-analysis of studies using any available functional method to examine differences in peripheral endothelial function between cirrhotic and non-cirrhotic individuals.
Methods
Literature search involved PubMed, Web-of-Science, and Scopus databases, as well as gray literature sources. We included studies in adult subjects evaluating endothelial function with any semi-invasive or non-invasive functional method in patients with and without liver cirrhosis.
Results
From 3378 records initially retrieved, 15 studies with a total of 570 participants were included in the final quantitative meta-analysis. In six studies examining endothelial function with flow-mediated-dilatation, no differences between patients with cirrhosis and controls were evident (WMD: 1.33, 95%CI [−2.87, 5.53], I2 = 97%, p < .00001). Among studies assessing differences in endothelial-dependent or endothelial-independent vasodilation with venous-occlusion-plethysmography, there were no significant differences between the two groups. When pooling all studies together, regardless of the technique used, no significant difference in endothelial function between cirrhotic patients and controls was observed(SMD: 0.79, 95%CI[−0.04, 1.63], I2 = 94%, p < .00001).
Conclusions
No differences in peripheral endothelial function assessed with semi-invasive or non-invasive functional methods exist between cirrhotic and non-cirrhotic subjects. The increasing co-existence of cardiovascular risk factors leading to impaired vascular reactivity in cirrhotic patients may partly explain these findings.
{"title":"Peripheral endothelial and microvascular damage in liver cirrhosis: A systematic review and meta-analysis","authors":"Ioanna Papagiouvanni, Marieta P. Theodorakopoulou, Pantelis A. Sarafidis, Emmanouil Sinakos, Ioannis Goulis","doi":"10.1111/micc.12773","DOIUrl":"10.1111/micc.12773","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>This is the first systematic review and meta-analysis of studies using any available functional method to examine differences in peripheral endothelial function between cirrhotic and non-cirrhotic individuals.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Literature search involved PubMed, Web-of-Science, and Scopus databases, as well as gray literature sources. We included studies in adult subjects evaluating endothelial function with any semi-invasive or non-invasive functional method in patients with and without liver cirrhosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>From 3378 records initially retrieved, 15 studies with a total of 570 participants were included in the final quantitative meta-analysis. In six studies examining endothelial function with flow-mediated-dilatation, no differences between patients with cirrhosis and controls were evident (WMD: 1.33, 95%CI [−2.87, 5.53], <i>I</i><sup>2</sup> = 97%, <i>p</i> < .00001). Among studies assessing differences in endothelial-dependent or endothelial-independent vasodilation with venous-occlusion-plethysmography, there were no significant differences between the two groups. When pooling all studies together, regardless of the technique used, no significant difference in endothelial function between cirrhotic patients and controls was observed(SMD: 0.79, 95%CI[−0.04, 1.63], <i>I</i><sup>2</sup> = 94%, <i>p</i> < .00001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>No differences in peripheral endothelial function assessed with semi-invasive or non-invasive functional methods exist between cirrhotic and non-cirrhotic subjects. The increasing co-existence of cardiovascular risk factors leading to impaired vascular reactivity in cirrhotic patients may partly explain these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 4-5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42149471","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}
Abeer Ahmed Abdelmaksoud, Shaymaa Maher Daifallah, Nouran Yousef Salah, Ahmed Salah Saber
Objectives
Microangiopathy is implicated in the pathogenesis of diabetic vascular complications. Nail fold videocapillaroscopy (NVC) is an easy non-invasive tool of microvasculature assessment. This study compares the NVC changes in adolescents with Type1 diabetes (T1D) to healthy controls and correlates them to diabetic vascular complications.
Methods
Hundred thirty-five adolescents with T1D (disease duration 5 years) were compared to 135 matched controls. Diabetes duration, insulin therapy, fundus, and Toronto clinical scoring system (TCSS) were assessed. Fasting lipids, fraction-C of glycosylated hemoglobin (HbA1C), urinary albumin creatinine ratio (UACR), nerve conduction velocity, and NVC were performed.
Results
NVC changes were found in 120 adolescents with T1D (88.8%). These changes were significantly higher in adolescents with T1D than controls (p < .001). Significant positive relation was found between NVC changes and TCSS (p = .006), diabetes duration (p = .001), HbA1C (0.008), cholesterol (p = .011), LDL (0.016), UACR (p < .001), and nerve conduction velocity (p < .001). Multivariate logistic regression study revealed that diabetic nephropathy and neuropathy were independently associated with NVC changes (p < .001 and p = .007, respectively).
Conclusion
Adolescents with T1D have significantly higher NVC changes than controls. These changes were more evident in those having vascular complications than those without. Thus, NVC can be a potential non-invasive tool for early assessment and follow-up of the microvasculature among adolescents with T1D.
{"title":"Nail fold microangiopathy in adolescents with type 1 diabetes: Relation to diabetic vascular complications","authors":"Abeer Ahmed Abdelmaksoud, Shaymaa Maher Daifallah, Nouran Yousef Salah, Ahmed Salah Saber","doi":"10.1111/micc.12771","DOIUrl":"10.1111/micc.12771","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Microangiopathy is implicated in the pathogenesis of diabetic vascular complications. Nail fold videocapillaroscopy (NVC) is an easy non-invasive tool of microvasculature assessment. This study compares the NVC changes in adolescents with Type1 diabetes (T1D) to healthy controls and correlates them to diabetic vascular complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Hundred thirty-five adolescents with T1D (disease duration 5 years) were compared to 135 matched controls. Diabetes duration, insulin therapy, fundus, and Toronto clinical scoring system (TCSS) were assessed. Fasting lipids, fraction-C of glycosylated hemoglobin (HbA1C), urinary albumin creatinine ratio (UACR), nerve conduction velocity, and NVC were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NVC changes were found in 120 adolescents with T1D (88.8%). These changes were significantly higher in adolescents with T1D than controls (<i>p</i> < .001). Significant positive relation was found between NVC changes and TCSS (<i>p</i> = .006), diabetes duration (<i>p</i> = .001), HbA1C (0.008), cholesterol (<i>p</i> = .011), LDL (0.016), UACR (<i>p</i> < .001), and nerve conduction velocity (<i>p</i> < .001). Multivariate logistic regression study revealed that diabetic nephropathy and neuropathy were independently associated with NVC changes (<i>p</i> < .001 and <i>p</i> = .007, respectively).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Adolescents with T1D have significantly higher NVC changes than controls. These changes were more evident in those having vascular complications than those without. Thus, NVC can be a potential non-invasive tool for early assessment and follow-up of the microvasculature among adolescents with T1D.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 6-7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10444696","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}
Rheumatoid arthritis (RA) is one of the most common chronic inflammatory joint disorders. While our understanding of the autoimmune processes that lead to synovial degradation has improved, a majority of patients are still resistant to current treatments and require new therapeutics. An understudied and promising area for therapy involves the roles of lymphatic vessels (LVs) in RA progression, which has been observed to have a significant effect on mediating chronic inflammation. RA disease progression has been shown to correlate with dramatic changes in LV structure and interstitial fluid drainage, manifesting in the retention of distinct immune cell phenotypes within the synovium. Advances in dynamic imaging technologies have demonstrated that LVs in RA undergo an initial expansion phase of increased LVs and abnormal contractions followed by a collapsed phase of reduced lymphatic function and immune cell clearance in vivo. However, current animal models of RA fail to decouple biological and biophysical factors that might be responsible for this lymphatic dysfunction in RA, and a few attempted in vitro models of the synovium in RA have not yet included the contributions from the LVs. Various methods of replicating LVs in vitro have been developed to study lymphatic biology, but these have yet not been integrated into the RA context. This review discusses the roles of LVs in RA and the current engineering approaches to improve our understanding of lymphatic pathophysiology in RA.
{"title":"Engineering approaches to investigate the roles of lymphatics vessels in rheumatoid arthritis","authors":"Samantha E. Kraus, Esak Lee","doi":"10.1111/micc.12769","DOIUrl":"10.1111/micc.12769","url":null,"abstract":"<p>Rheumatoid arthritis (RA) is one of the most common chronic inflammatory joint disorders. While our understanding of the autoimmune processes that lead to synovial degradation has improved, a majority of patients are still resistant to current treatments and require new therapeutics. An understudied and promising area for therapy involves the roles of lymphatic vessels (LVs) in RA progression, which has been observed to have a significant effect on mediating chronic inflammation. RA disease progression has been shown to correlate with dramatic changes in LV structure and interstitial fluid drainage, manifesting in the retention of distinct immune cell phenotypes within the synovium. Advances in dynamic imaging technologies have demonstrated that LVs in RA undergo an initial expansion phase of increased LVs and abnormal contractions followed by a collapsed phase of reduced lymphatic function and immune cell clearance in vivo. However, current animal models of RA fail to decouple biological and biophysical factors that might be responsible for this lymphatic dysfunction in RA, and a few attempted in vitro models of the synovium in RA have not yet included the contributions from the LVs. Various methods of replicating LVs in vitro have been developed to study lymphatic biology, but these have yet not been integrated into the RA context. This review discusses the roles of LVs in RA and the current engineering approaches to improve our understanding of lymphatic pathophysiology in RA.</p>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"30 2-3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9684355/pdf/nihms-1820293.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9488852","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}
Fariba Aghabaglou, Ana Ainechi, Haley Abramson, Eli Curry, Tarana Parvez Kaovasia, Serene Kamal, Molly Acord, Smruti Mahapatra, Aliaksei Pustavoitau, Beth Smith, Javad Azadi, Jennifer K. Son, Ian Suk, Nicholas Theodore, Betty M. Tyler, Amir Manbachi
Objective
Monitoring microcirculation and visualizing microvasculature are critical for providing diagnosis to medical professionals and guiding clinical interventions. Ultrasound provides a medium for monitoring and visualization; however, there are challenges due to the complex microscale geometry of the vasculature and difficulties associated with quantifying perfusion. Here, we studied established and state-of-the-art ultrasonic modalities (using six probes) to compare their detection of slow flow in small microvasculature.
Methods
Five ultrasonic modalities were studied: grayscale, color Doppler, power Doppler, superb microvascular imaging (SMI), and microflow imaging (MFI), using six linear probes across two ultrasound scanners. Image readability was blindly scored by radiologists and quantified for evaluation. Vasculature visualization was investigated both in vitro (resolution and flow characterization) and in vivo (fingertip microvasculature detection).
Results
Superb Microvascular Imaging (SMI) and Micro Flow Imaging (MFI) modalities provided superior images when compared with conventional ultrasound imaging modalities both in vitro and in vivo. The choice of probe played a significant difference in detectability. The slowest flow detected (in the lab) was 0.1885 ml/s and small microvasculature of the fingertip were visualized.
Conclusions
Our data demonstrated that SMI and MFI used with vascular probes operating at higher frequencies provided resolutions acceptable for microvasculature visualization, paving the path for future development of ultrasound devices for microcirculation monitoring.
{"title":"Ultrasound monitoring of microcirculation: An original study from the laboratory bench to the clinic","authors":"Fariba Aghabaglou, Ana Ainechi, Haley Abramson, Eli Curry, Tarana Parvez Kaovasia, Serene Kamal, Molly Acord, Smruti Mahapatra, Aliaksei Pustavoitau, Beth Smith, Javad Azadi, Jennifer K. Son, Ian Suk, Nicholas Theodore, Betty M. Tyler, Amir Manbachi","doi":"10.1111/micc.12770","DOIUrl":"10.1111/micc.12770","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Monitoring microcirculation and visualizing microvasculature are critical for providing diagnosis to medical professionals and guiding clinical interventions. Ultrasound provides a medium for monitoring and visualization; however, there are challenges due to the complex microscale geometry of the vasculature and difficulties associated with quantifying perfusion. Here, we studied established and state-of-the-art ultrasonic modalities (using six probes) to compare their detection of slow flow in small microvasculature.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Five ultrasonic modalities were studied: grayscale, color Doppler, power Doppler, superb microvascular imaging (SMI), and microflow imaging (MFI), using six linear probes across two ultrasound scanners. Image readability was blindly scored by radiologists and quantified for evaluation. Vasculature visualization was investigated both in vitro (resolution and flow characterization) and in vivo (fingertip microvasculature detection).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Superb Microvascular Imaging (SMI) and Micro Flow Imaging (MFI) modalities provided superior images when compared with conventional ultrasound imaging modalities both in vitro and in vivo. The choice of probe played a significant difference in detectability. The slowest flow detected (in the lab) was 0.1885 ml/s and small microvasculature of the fingertip were visualized.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our data demonstrated that SMI and MFI used with vascular probes operating at higher frequencies provided resolutions acceptable for microvasculature visualization, paving the path for future development of ultrasound devices for microcirculation monitoring.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18459,"journal":{"name":"Microcirculation","volume":"29 6-7","pages":""},"PeriodicalIF":2.4,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/91/2a/MICC-29-e12770.PMC9786257.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10444693","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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