Amalia Baroutidou, Theodoros Dimitroulas, Alexandra Arvanitaki, Triantafyllia Grantza, Nikolaos Otountzidis, Ioannis T Farmakis, Artemios G Karagiannidis, Vasileios Kamperidis, Antonios Ziakas, Pantelis Sarafidis, George Giannakoulas
Background: Adults with congenital heart disease (ACHD) can face a lifelong risk of premature cardiovascular events. Endothelial dysfunction and arterial stiffness may be some of the key mechanisms involved. Early identification of endothelial damage in ACHD could be crucial to mitigate the adverse events. This systematic review and meta-analysis aims to investigate micro- and macroangiopathy in ACHD.
Methods: We systematically searched four major electronic databases (PubMed, CENTRAL, Scopus and Web of Science), ClinicalTrials.gov and grey literature according to PRISMA guidelines. We included studies evaluating endothelial function with any semi- or non-invasive method in ACHD and healthy controls. Studies exploring arterial stiffness indices and carotid intima-media thickness were also investigated.
Results: In total, 31 studies (1118 ACHD, 794 controls) were included in this systematic review. Brachial artery endothelium-dependent (assessed via flow-mediated dilatation, FMD) and -independent vasodilation (assessed via nitroglycerine-mediated dilatation, NMD) were attenuated in ACHD versus controls (mean difference [MD] -2.5, 95% confidence intervals [CI] -3.7; -1.3 and MD -3.9, 95% CI -6.8; -1.0, respectively). ACHD also demonstrated impaired microvascular function, evaluated via peripheral arterial tonometry (PAT), with significantly lower reactive hyperemia index and PAT ratio compared to controls (MD -.26, 95% CI -.48; -.04 and MD -.4, 95% CI -.5; -.4, respectively). Regarding arterial stiffness, pooled analysis revealed non-significant differences in pulse wave velocity between the study groups (standardized MD .2, 95% CI -.2; .6). However, the augmentation index was significantly higher in ACHD (standardized MD 1.6, 95% CI .8; 2.4).
Conclusions: ACHD exhibit impaired macro- and microvascular function and elevated arterial stiffness, factors that may be responsible for the increased adverse cardiovascular events in this population.
背景：患有先天性心脏病（ACHD）的成年人可能面临终生过早心血管事件的风险。内皮功能障碍和动脉僵硬可能是其中的一些关键机制。早期识别血管内皮损伤对减轻不良事件至关重要。本系统综述和荟萃分析旨在探讨ACHD的微血管和大血管病变。方法：根据PRISMA指南系统检索PubMed、CENTRAL、Scopus和Web of Science四大电子数据库、ClinicalTrials.gov和灰色文献。我们纳入了用半侵入性或非侵入性方法评估ACHD患者和健康对照者内皮功能的研究。研究探讨了动脉硬度指数和颈动脉内膜-中膜厚度。结果：本系统综述共纳入31项研究（1118例ACHD， 794例对照）。与对照组相比，ACHD患者肱动脉内皮依赖性（通过血流介导的扩张，FMD评估）和非依赖性血管扩张（通过硝酸甘油介导的扩张，NMD评估）减弱(平均差[MD] -2.5, 95%可信区间[CI] -3.7；-1.3和MD -3.9, 95% CI -6.8；分别为-1.0)。通过外周动脉血压计（PAT）评估，ACHD还表现出微血管功能受损，与对照组相比，反应性充血指数和PAT比率显著降低（MD -）。26, 95% ci - 0.48；－．04和MD -。4.95% ci - 0.5；－．分别为4)。关于动脉硬度，合并分析显示各组间脉波速度无显著差异(标准化MD .2, 95% CI - 2；6)。然而，ACHD的增强指数明显更高(标准化MD 1.6, 95% CI .8；2.4)。结论：ACHD表现出宏观和微血管功能受损以及动脉僵硬度升高，这些因素可能导致该人群中不良心血管事件的增加。
{"title":"Endothelial dysfunction in adults with congenital heart disease: A systematic review and meta-analysis.","authors":"Amalia Baroutidou, Theodoros Dimitroulas, Alexandra Arvanitaki, Triantafyllia Grantza, Nikolaos Otountzidis, Ioannis T Farmakis, Artemios G Karagiannidis, Vasileios Kamperidis, Antonios Ziakas, Pantelis Sarafidis, George Giannakoulas","doi":"10.1111/eci.14376","DOIUrl":"https://doi.org/10.1111/eci.14376","url":null,"abstract":"<p><strong>Background: </strong>Adults with congenital heart disease (ACHD) can face a lifelong risk of premature cardiovascular events. Endothelial dysfunction and arterial stiffness may be some of the key mechanisms involved. Early identification of endothelial damage in ACHD could be crucial to mitigate the adverse events. This systematic review and meta-analysis aims to investigate micro- and macroangiopathy in ACHD.</p><p><strong>Methods: </strong>We systematically searched four major electronic databases (PubMed, CENTRAL, Scopus and Web of Science), ClinicalTrials.gov and grey literature according to PRISMA guidelines. We included studies evaluating endothelial function with any semi- or non-invasive method in ACHD and healthy controls. Studies exploring arterial stiffness indices and carotid intima-media thickness were also investigated.</p><p><strong>Results: </strong>In total, 31 studies (1118 ACHD, 794 controls) were included in this systematic review. Brachial artery endothelium-dependent (assessed via flow-mediated dilatation, FMD) and -independent vasodilation (assessed via nitroglycerine-mediated dilatation, NMD) were attenuated in ACHD versus controls (mean difference [MD] -2.5, 95% confidence intervals [CI] -3.7; -1.3 and MD -3.9, 95% CI -6.8; -1.0, respectively). ACHD also demonstrated impaired microvascular function, evaluated via peripheral arterial tonometry (PAT), with significantly lower reactive hyperemia index and PAT ratio compared to controls (MD -.26, 95% CI -.48; -.04 and MD -.4, 95% CI -.5; -.4, respectively). Regarding arterial stiffness, pooled analysis revealed non-significant differences in pulse wave velocity between the study groups (standardized MD .2, 95% CI -.2; .6). However, the augmentation index was significantly higher in ACHD (standardized MD 1.6, 95% CI .8; 2.4).</p><p><strong>Conclusions: </strong>ACHD exhibit impaired macro- and microvascular function and elevated arterial stiffness, factors that may be responsible for the increased adverse cardiovascular events in this population.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":" ","pages":"e14376"},"PeriodicalIF":4.4,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
New-onset atrial fibrillation (AF) is associated with an increased risk of stroke in hospitalized patients with severe sepsis. Post-cardiac arrest patients experience conditions similar to sepsis. This study investigated whether pre-arrest AF is associated with poor neurological recovery following in-hospital cardiac arrest (IHCA).
Methods
This single-centre retrospective study included patients experiencing IHCA between 2005 and 2020. Pre-arrest electrocardiograms (ECGs) were reviewed, including twelve-lead ECGs and ECG strips. New-onset AF was defined as AF absent on electronic health records (EHRs, including admission diagnosis, past medical history and hospitalization notes) but present on pre-arrest ECG. Without considering EHRs, AF-presence was defined as AF present on pre-arrest ECG.
Results
A total of 2466 patients were included, including 93 (3.8%) with new-onset AF and 131 (5.3%) with evidence of AF on pre-arrest ECG. The median age was 67.6 (interquartile range [IQR]: 22.3) years and the median CHA₂DS₂-VASc score was 3.0 (IQR: 3.0). A total of 405 (16.4%) patients survived to hospital discharge, with 228 (9.2%) patients achieving favourable neurological recovery. Multivariable logistic regression analysis indicated that both new-onset AF (odds ratio [OR]: .34, 95% confidence interval [CI]: .12–.94, p-value: .04) and AF-presence (OR: .35, 95% CI: .15–.85, p-value: .02) were inversely associated with favourable neurological recovery in the primary and sensitivity analyses, respectively.
Conclusions
Pre-arrest AF is a significant risk factor for poor neurological recovery following IHCA. Further research is needed to understand the underlying mechanisms, which could inform the development of strategies to improve outcomes in this patient subgroup.
{"title":"Pre-arrest atrial fibrillation and neurological recovery after cardiac arrest among hospitalized patients: A retrospective cohort study","authors":"Chih-Hung Wang, Yan-Yu Chen, Meng-Che Wu, Li-Ting Ho, Cheng-Yi Wu, Joyce Tay, Wei-Han Lin, Jr-Jiun Lin, Huang-Fu Yeh, Yen-Wen Wu, Chien-Hua Huang, Wen-Jone Chen","doi":"10.1111/eci.14375","DOIUrl":"10.1111/eci.14375","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>New-onset atrial fibrillation (AF) is associated with an increased risk of stroke in hospitalized patients with severe sepsis. Post-cardiac arrest patients experience conditions similar to sepsis. This study investigated whether pre-arrest AF is associated with poor neurological recovery following in-hospital cardiac arrest (IHCA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This single-centre retrospective study included patients experiencing IHCA between 2005 and 2020. Pre-arrest electrocardiograms (ECGs) were reviewed, including twelve-lead ECGs and ECG strips. New-onset AF was defined as AF absent on electronic health records (EHRs, including admission diagnosis, past medical history and hospitalization notes) but present on pre-arrest ECG. Without considering EHRs, AF-presence was defined as AF present on pre-arrest ECG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 2466 patients were included, including 93 (3.8%) with new-onset AF and 131 (5.3%) with evidence of AF on pre-arrest ECG. The median age was 67.6 (interquartile range [IQR]: 22.3) years and the median CHA₂DS₂-VASc score was 3.0 (IQR: 3.0). A total of 405 (16.4%) patients survived to hospital discharge, with 228 (9.2%) patients achieving favourable neurological recovery. Multivariable logistic regression analysis indicated that both new-onset AF (odds ratio [OR]: .34, 95% confidence interval [CI]: .12–.94, <i>p</i>-value: .04) and AF-presence (OR: .35, 95% CI: .15–.85, <i>p</i>-value: .02) were inversely associated with favourable neurological recovery in the primary and sensitivity analyses, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Pre-arrest AF is a significant risk factor for poor neurological recovery following IHCA. Further research is needed to understand the underlying mechanisms, which could inform the development of strategies to improve outcomes in this patient subgroup.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Laura Schnetzer, Andreas Leiherer, Andreas Festa, Axel Mündlein, Thomas Plattner, Gert Mayer, Christoph Saely, Heinz Drexel
Background
Both chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) confer a high risk of cardiovascular disease and mortality. These entities frequently coincide. The separate and joint impact of CKD and T2DM on the risk of major cardiovascular events (MACE) and survival is unclear.
Methods
In this prospective cohort study, patients with angiographically proven coronary artery disease were investigated according to their CKD and T2DM status (T2DM−/CKD−, T2DM+/CKD−, T2DM−/CKD+, T2DM+/CKD+) and followed for up to 18 years.
Results
A total of 1441 patients were included in the study of whom 39% experienced MACE (T2DM−/CKD−: 31%, T2DM+/CKD−: 43%, T2DM−/CKD+: 53%, T2DM+/CKD+: 61%) and 53% died. A log-rank test revealed significant differences between the event-free time period of the four groups (χ2 (3) = 112.57, p < 0.001). The presence of T2DM and CKD was associated with a 2.72-fold increase [1.98–3.73] in MACE compared to patients who suffered from neither condition (p < 0.001). T2DM alone led to a 1.37-fold increase [1.1–1.7], (p = 0.004), CKD alone to a 1.71-fold increase [1.31–2.25], (p < 0.001).
Conclusion
T2DM and CKD in patients with coronary artery disease are mutually independent predictors of cardiovascular events. Patients with both CKD and T2DM are at an extremely high risk for cardiovascular events.
{"title":"Type 2 diabetes and chronic kidney disease as long-term predictors of cardiovascular events in patients with coronary artery disease","authors":"Laura Schnetzer, Andreas Leiherer, Andreas Festa, Axel Mündlein, Thomas Plattner, Gert Mayer, Christoph Saely, Heinz Drexel","doi":"10.1111/eci.14374","DOIUrl":"10.1111/eci.14374","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Both chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM) confer a high risk of cardiovascular disease and mortality. These entities frequently coincide. The separate and joint impact of CKD and T2DM on the risk of major cardiovascular events (MACE) and survival is unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective cohort study, patients with angiographically proven coronary artery disease were investigated according to their CKD and T2DM status (T2DM−/CKD−, T2DM+/CKD−, T2DM−/CKD+, T2DM+/CKD+) and followed for up to 18 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1441 patients were included in the study of whom 39% experienced MACE (T2DM−/CKD−: 31%, T2DM+/CKD−: 43%, T2DM−/CKD+: 53%, T2DM+/CKD+: 61%) and 53% died. A log-rank test revealed significant differences between the event-free time period of the four groups (<i>χ</i><sup>2</sup> (3) = 112.57, <i>p</i> < 0.001). The presence of T2DM and CKD was associated with a 2.72-fold increase [1.98–3.73] in MACE compared to patients who suffered from neither condition (<i>p</i> < 0.001). T2DM alone led to a 1.37-fold increase [1.1–1.7], (<i>p</i> = 0.004), CKD alone to a 1.71-fold increase [1.31–2.25], (<i>p</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>T2DM and CKD in patients with coronary artery disease are mutually independent predictors of cardiovascular events. Patients with both CKD and T2DM are at an extremely high risk for cardiovascular events.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 3","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inflammation, lipids and cardiovascular risk: The quest for improving risk stratification and prognosis in ischemic heart disease","authors":"Giulio Francesco Romiti, Giovanni Buoninfante, Stefania Basili","doi":"10.1111/eci.14373","DOIUrl":"10.1111/eci.14373","url":null,"abstract":"<p>Lp(a): Lipoprotein (a). Created in BioRender. Romiti, G. (2024) BioRender.com/g02a734.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 4","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CEACAM1 in leukocytes controls cell activation during inflammation. This and its expression in epithelial cells led to frequent independent appropriation of CEACAM1 as receptor by pathogens in humans and other species to gain host access and to downregulate its immune response. As a countermeasure, decoy receptors with CEACAM1-like pathogen-binding domains evolved. The granulocyte-specific human CEACAM3 endocytic receptor diverts CEACAM1-binding pathogens to neutrophils for internalization and destruction. The role of the glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 which can also bind CEACAM1-targeting pathogens in humans is less clear.
Methods
We analyzed the selection of CEACAMs to avoid pathogen binding and to maintain similarity between pathogen receptors and decoy receptors in 148 primate species.
Results
Notably, functional CEACAM3 genes were not found in gibbons and New World monkeys. Interestingly, CEACAM6 in these primates exhibits similar high ratios of rates of nonsynonymous and synonymous substitution (dN/dS) in their pathogen-binding N domain exons as found for CEACAM1. High dN/dS ratios are indicative of selection for diversification typically seen in pathogen receptors. Human CEACAM6 is expressed on granulocytes and epithelial cells. Therefore, CEACAM6 could substitute for the missing endocytic receptor CEACAM3. In nearly all investigated primate groups also N exons of the epithelially expressed CEACAM5 exhibit selection for diversification. In African populations, five high-frequency polymorphisms are observed in the pathogen-binding region of CEACAM5 (I80V, V83A, I100T, I112V, I113T) with 3-4 polymorphisms combined in the same individual. These polymorphisms correspond to CEACAM1 pathogen-binding domain sequences.
Conclusion
The glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 are under selection to maintain similarity to the pathogen receptor CEACAM1 in most primate species, indicating a function as decoy receptors.
{"title":"Evolution of CEACAM pathogen decoy receptors in primates","authors":"Wolfgang Zimmermann, Robert Kammerer","doi":"10.1111/eci.14356","DOIUrl":"10.1111/eci.14356","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>CEACAM1 in leukocytes controls cell activation during inflammation. This and its expression in epithelial cells led to frequent independent appropriation of CEACAM1 as receptor by pathogens in humans and other species to gain host access and to downregulate its immune response. As a countermeasure, decoy receptors with CEACAM1-like pathogen-binding domains evolved. The granulocyte-specific human CEACAM3 endocytic receptor diverts CEACAM1-binding pathogens to neutrophils for internalization and destruction. The role of the glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 which can also bind CEACAM1-targeting pathogens in humans is less clear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed the selection of CEACAMs to avoid pathogen binding and to maintain similarity between pathogen receptors and decoy receptors in 148 primate species.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Notably, functional CEACAM3 genes were not found in gibbons and New World monkeys. Interestingly, CEACAM6 in these primates exhibits similar high ratios of rates of nonsynonymous and synonymous substitution (dN/dS) in their pathogen-binding N domain exons as found for <i>CEACAM1</i>. High dN/dS ratios are indicative of selection for diversification typically seen in pathogen receptors. Human CEACAM6 is expressed on granulocytes and epithelial cells. Therefore, CEACAM6 could substitute for the missing endocytic receptor CEACAM3. In nearly all investigated primate groups also N exons of the epithelially expressed CEACAM5 exhibit selection for diversification. In African populations, five high-frequency polymorphisms are observed in the pathogen-binding region of CEACAM5 (I80V, V83A, I100T, I112V, I113T) with 3-4 polymorphisms combined in the same individual. These polymorphisms correspond to CEACAM1 pathogen-binding domain sequences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The glycosylphosphatidylinositol-anchored CEACAM5 and CEACAM6 are under selection to maintain similarity to the pathogen receptor CEACAM1 in most primate species, indicating a function as decoy receptors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James M. Fleckenstein, Sonia M. Najjar, Wolfgang Zimmermann, Christof R. Hauck, Quynh Nguyen, Raquel Mejias-Luque, Asima Bhattacharyya, Alex J. McCarthy, Arup Sarkar, Maciej Kujawski, Anastasia Konieva, Fadi Elyateem, Irina Kube-Golovin, Gunther Wennemuth, Robert Kammerer, Keith M. Skubitz, John E. Shively, Kenneth J. Dery, Gabriela Dveksler, Lisa Götz, Florian Kleefeldt, Süleyman Ergün
{"title":"Current investigation of carcinoembryonic antigen cell adhesion molecule (CEACAM) biology summary of the 32nd CEA symposium: 20–23 September 2024. Würzburg, Germany","authors":"James M. Fleckenstein, Sonia M. Najjar, Wolfgang Zimmermann, Christof R. Hauck, Quynh Nguyen, Raquel Mejias-Luque, Asima Bhattacharyya, Alex J. McCarthy, Arup Sarkar, Maciej Kujawski, Anastasia Konieva, Fadi Elyateem, Irina Kube-Golovin, Gunther Wennemuth, Robert Kammerer, Keith M. Skubitz, John E. Shively, Kenneth J. Dery, Gabriela Dveksler, Lisa Götz, Florian Kleefeldt, Süleyman Ergün","doi":"10.1111/eci.14355","DOIUrl":"10.1111/eci.14355","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The hypoxic microenvironment is a key component of the gastric tumour niche. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is upregulated in gastric cancer and is considered a novel biomarker for the disease. However, no prior studies have elaborated on the status of CEACAM6 and its role in the hypoxic gastric cancer niche.
Methods
In this short study, we evaluated the effect of hypoxia in modulating CEACAM6 level in gastric cancer cells (GCCs) through western blotting and determined the effect of CEACAM6 upregulation on gastric cancer progression through clonogenicity, cell proliferation and migration assays. The wound-healing ability of GCCs was downregulated by siRNA-mediated CEACAM6 silencing. Human gastric cancer biopsy samples were examined by immunofluorescence microscopy to assess the level of a hypoxia marker HIF1α and CEACAM6. The effect of empty vector or CEACAM6-expression on peripheral blood-derived mononuclear cell (PBMC)-derived macrophage polarization under normoxia or hypoxia was studied by incubating macrophages in conditioned medium collected from GCC cultures. Macrophage polarization status was observed using flow cytometry and fluorescence microscopy. Reactive oxygen species (ROS) generation by macrophages was evaluated using fluorescence microscopy.
Results
We identified that hypoxia promoted CEACAM6 in GCCs, and these cells acquired increased proliferative potential and migration ability. Moreover, the cell culture supernatant from hypoxia-exposed CEACAM6-overexpressing cells promoted an M2-like macrophage population and discouraged the M1 phenotype.
Conclusion
This study established that hypoxia increased CEACAM6 which promoted gastric cancer progression by influencing GCC proliferation and motility as well as macrophage polarization.
{"title":"The influence of hypoxia-mediated CEACAM6 upregulation on epithelial cell and macrophage response in the context of gastric cancer","authors":"Indrajit Poirah, Debashish Chakraborty, Pragyesh Dixit, Supriya Samal, Smaran Banerjee, Tathagata Mukherjee, Subhasis Chattopadhyay, Gautam Nath, Asima Bhattacharyya","doi":"10.1111/eci.14352","DOIUrl":"10.1111/eci.14352","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The hypoxic microenvironment is a key component of the gastric tumour niche. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is upregulated in gastric cancer and is considered a novel biomarker for the disease. However, no prior studies have elaborated on the status of CEACAM6 and its role in the hypoxic gastric cancer niche.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this short study, we evaluated the effect of hypoxia in modulating CEACAM6 level in gastric cancer cells (GCCs) through western blotting and determined the effect of CEACAM6 upregulation on gastric cancer progression through clonogenicity, cell proliferation and migration assays. The wound-healing ability of GCCs was downregulated by siRNA-mediated <i>CEACAM6</i> silencing. Human gastric cancer biopsy samples were examined by immunofluorescence microscopy to assess the level of a hypoxia marker HIF1α and CEACAM6. The effect of empty vector or <i>CEACAM6-</i>expression on peripheral blood-derived mononuclear cell (PBMC)-derived macrophage polarization under normoxia or hypoxia was studied by incubating macrophages in conditioned medium collected from GCC cultures. Macrophage polarization status was observed using flow cytometry and fluorescence microscopy. Reactive oxygen species (ROS) generation by macrophages was evaluated using fluorescence microscopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We identified that hypoxia promoted CEACAM6 in GCCs, and these cells acquired increased proliferative potential and migration ability. Moreover, the cell culture supernatant from hypoxia-exposed CEACAM6-overexpressing cells promoted an M2-like macrophage population and discouraged the M1 phenotype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study established that hypoxia increased CEACAM6 which promoted gastric cancer progression by influencing GCC proliferation and motility as well as macrophage polarization.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reciprocity between the regulation of the expression and functions of CEACAM","authors":"Sonia M. Najjar, M. Paula Macedo","doi":"10.1111/eci.14362","DOIUrl":"10.1111/eci.14362","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In addition to the long-known antibacterial actions of neutrophils, neutrophils are recognized to have a variety of other effects and are functionally diverse. Neutrophils can either stimulate or inhibit B cells and T cells, regulate NK development and activity, augment or direct the resolution of inflammation, act as myeloid-derived suppressor cells, modulate tumour growth and metastasis and trigger autoimmune diseases. CEACAMs 1, 3, 6 and 8 are expressed on human neutrophils.
Methods
A literature review was performed on the role of CEACAMs in neutrophil function.
Results
CEACAMs 1, 6 and 8 can be upregulated from intracellular stores, while CEACAM3, an opsonin-independent phagocytic receptor, is constitutively expressed. CEACAM1 has an intracellular ITIM motif and an ITSM motif, and CEACAM3 has an ITAM-like motif; CEACAMs 6 and 8 are glycosylphosphatidylinositol-linked. CEACAM8 can also be released in a soluble form. These CEACAMs can interact with multiple other host CEACAMs as well as other molecules on bacteria, fungi and host cells, both transmitting and receiving signals. Known CEACAM-binding pathogens bind the CFG face of the N domain which is also important in CEACAM-CEACAM binding, although the ABDE face also appears to be involved in higher-order oligomers.
Conclusions
Understanding the exact role of each individual CEACAM in human neutrophils is complicated by the fact that the neutrophil CEACAMs can interact with multiple ligands. The data demonstrates some of the many roles of CEACAMs in neutrophil function and the extensive role of the neutrophil in human biology beyond its classical role as a short-lived phagocyte.
{"title":"The role of CEACAMs in neutrophil function","authors":"Keith M. Skubitz","doi":"10.1111/eci.14349","DOIUrl":"10.1111/eci.14349","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>In addition to the long-known antibacterial actions of neutrophils, neutrophils are recognized to have a variety of other effects and are functionally diverse. Neutrophils can either stimulate or inhibit B cells and T cells, regulate NK development and activity, augment or direct the resolution of inflammation, act as myeloid-derived suppressor cells, modulate tumour growth and metastasis and trigger autoimmune diseases. CEACAMs 1, 3, 6 and 8 are expressed on human neutrophils.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A literature review was performed on the role of CEACAMs in neutrophil function.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CEACAMs 1, 6 and 8 can be upregulated from intracellular stores, while CEACAM3, an opsonin-independent phagocytic receptor, is constitutively expressed. CEACAM1 has an intracellular ITIM motif and an ITSM motif, and CEACAM3 has an ITAM-like motif; CEACAMs 6 and 8 are glycosylphosphatidylinositol-linked. CEACAM8 can also be released in a soluble form. These CEACAMs can interact with multiple other host CEACAMs as well as other molecules on bacteria, fungi and host cells, both transmitting and receiving signals. Known CEACAM-binding pathogens bind the CFG face of the N domain which is also important in CEACAM-CEACAM binding, although the ABDE face also appears to be involved in higher-order oligomers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Understanding the exact role of each individual CEACAM in human neutrophils is complicated by the fact that the neutrophil CEACAMs can interact with multiple ligands. The data demonstrates some of the many roles of CEACAMs in neutrophil function and the extensive role of the neutrophil in human biology beyond its classical role as a short-lived phagocyte.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisa Götz, Uwe Rueckschloss, Süleyman Ergün, Florian Kleefeldt
Introduction
The glycoprotein Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin superfamily. It is expressed in a variety of tissues including epithelial, immune, as well as endothelial cells, and is crucial to diverse physiological and pathological mechanisms. This review aims to provide a comprehensive understanding of CEACAM1's multifaceted roles in vascular biology and inflammatory processes.
Methods
Directed literature research was conducted using databases, such as PubMed, and relevant studies were categorized based on the physiological effects of CEACAM1.
Results
CEACAM1 plays a pivotal role in vascular homeostasis, particularly influencing the formation, maturation, and aging of blood vessels, as well as the endothelial barrier function. It supports endothelium-dependent vasodilation and nitric oxide formation, thus promoting vascular integrity and regulating blood pressure. Additionally, CEACAM1 is of emerging importance to vascular inflammation and its potential clinical consequences.
Conclusion
CEACAM1 is a crucial regulator of vascular homeostasis and inflammation with significant implications for cardiovascular health. Despite the lack of understanding of tissue-specific modulation and isoform-dependent mechanisms, CEACAM1 could be a promising therapeutic target for the prevention of cardiovascular disease in the future.
{"title":"CEACAM1 in vascular homeostasis and inflammation","authors":"Lisa Götz, Uwe Rueckschloss, Süleyman Ergün, Florian Kleefeldt","doi":"10.1111/eci.14345","DOIUrl":"10.1111/eci.14345","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The glycoprotein Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin superfamily. It is expressed in a variety of tissues including epithelial, immune, as well as endothelial cells, and is crucial to diverse physiological and pathological mechanisms. This review aims to provide a comprehensive understanding of CEACAM1's multifaceted roles in vascular biology and inflammatory processes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Directed literature research was conducted using databases, such as PubMed, and relevant studies were categorized based on the physiological effects of CEACAM1.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>CEACAM1 plays a pivotal role in vascular homeostasis, particularly influencing the formation, maturation, and aging of blood vessels, as well as the endothelial barrier function. It supports endothelium-dependent vasodilation and nitric oxide formation, thus promoting vascular integrity and regulating blood pressure. Additionally, CEACAM1 is of emerging importance to vascular inflammation and its potential clinical consequences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>CEACAM1 is a crucial regulator of vascular homeostasis and inflammation with significant implications for cardiovascular health. Despite the lack of understanding of tissue-specific modulation and isoform-dependent mechanisms, CEACAM1 could be a promising therapeutic target for the prevention of cardiovascular disease in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"54 S2","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11646292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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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