Current Opinion in Hematology最新文献_第3页

Control of inflammatory lung injury and repair by metabolic signaling in endothelial cells. 内皮细胞代谢信号控制肺部炎症损伤和修复

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-10-18 DOI: 10.1097/MOH.0000000000000848

Seth Gould, Ansley Herron, Jonathan Davis, Mollie Phillips, Mrinmay Chakrabarti, Colin E Evans

{"title":"Control of inflammatory lung injury and repair by metabolic signaling in endothelial cells.","authors":"Seth Gould, Ansley Herron, Jonathan Davis, Mollie Phillips, Mrinmay Chakrabarti, Colin E Evans","doi":"10.1097/MOH.0000000000000848","DOIUrl":"https://doi.org/10.1097/MOH.0000000000000848","url":null,"abstract":"Purpose of review: Sepsis-induced inflammatory lung injury includes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). There are currently no effective treatments for ALI/ARDS, but clinical outcomes could be improved by inhibiting lung injury and/or promoting post-sepsis vascular repair. In this review, we describe studies of endothelial cell metabolic pathways in sepsis-induced ALI/ARDS and vascular repair and identify areas of research that deserve attention in future studies. We also describe studies of metabolic interventions that aim to inhibit ALI/ARDS and/or promote post-sepsis vascular repair, including those that target endothelial cell metabolites, endothelial cell metabolic signaling pathways, and endothelial cell metabolism.Recent findings: Endothelial cells are integral to both the injury and repair phases of ALI/ARDS. During the injury phase of ALI/ARDS, lung endothelial cell survival decreases, and lung endothelial cell-to-endothelial cell (EC-EC) junctions are weakened. During the repair phase after sepsis-induced lung injury, lung endothelial cell proliferation and lung EC-EC junction reannealing occur. These crucial aspects of ALI/ARDS and post-sepsis vascular repair, that is, endothelial cell viability, growth, and junction integrity, are controlled by a myriad of metabolites and metabolic signaling pathways in endothelial cells.Summary: Metabolic signaling pathways in endothelial cells represent a novel class of putative targets for the prevention and treatment of sepsis-induced inflammatory lung injury. Therapies that target metabolic signaling in endothelial cells are currently being explored as potential treatments for sepsis-induced inflammatory lung injury.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513343","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}

引用次数: 0

Editorial introduction. 编辑介绍。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-09-01 Epub Date: 2024-08-01 DOI: 10.1097/MOH.0000000000000829

引用次数: 0

Improving our understanding on the clinical role of plasmin-mediated von Willebrand factor degradation. 进一步了解由 plasmin 介导的 von Willebrand 因子降解的临床作用。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-09-01 Epub Date: 2024-05-03 DOI: 10.1097/MOH.0000000000000825

Hinde El Otmani, Karen Vanhoorelbeke, Claudia Tersteeg

{"title":"Improving our understanding on the clinical role of plasmin-mediated von Willebrand factor degradation.","authors":"Hinde El Otmani, Karen Vanhoorelbeke, Claudia Tersteeg","doi":"10.1097/MOH.0000000000000825","DOIUrl":"10.1097/MOH.0000000000000825","url":null,"abstract":"Purpose of review: Von Willebrand factor (VWF) plays a pivotal role in primary hemostasis. A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13 (ADAMTS13) is primarily responsible for cleaving ultra-large VWF multimers into smaller, less adhesive forms. However, plasmin has also been shown to cleave VWF multimers. This proteolytic cleavage of VWF results in a decreased multimer size and, hence, a lower VWF activity. This review aims to present a comprehensive overview of the involvement of plasmin-mediated VWF proteolysis in (micro)thrombosis.Recent findings: Plasmin-mediated VWF proteolysis has been suggested to play a role in various pathologies involving microthrombosis in combination with an imbalance in VWF antigen levels and ADAMTS13 activity, as well as activation of the fibrinolytic system, but quantitative assays to demonstrate this were lacking. Recently, a V H H-based bioassay was developed designed specifically to quantify plasmin-cleaved VWF (cVWF). The novel ELISA assay holds significant promise for gaining further insights into the clinical relevance of plasmin-mediated VWF proteolysis in several pathologies. Furthermore, local plasmin activation at the site of microthrombosis has been shown to be a promising treatment strategy by degrading VWF-rich microthrombi.Summary: Plasmin-mediated proteolysis of VWF is observed during microthrombosis; however, it remains unclear whether it impacts disease severity. A novel ELISA method to detect cVWF will improve our understanding of the clinical role of plasmin-mediated VWF degradation.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"245-250"},"PeriodicalIF":3.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900445","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}

引用次数: 0

Histon activities in the extracellular environment: regulation and prothrombotic implications. 细胞外环境中的组蛋白活性：调节和促血栓形成的影响。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-09-01 Epub Date: 2024-05-27 DOI: 10.1097/MOH.0000000000000827

Gwen M Keulen, Joram Huckriede, Kanin Wichapong, Gerry A F Nicolaes

{"title":"Histon activities in the extracellular environment: regulation and prothrombotic implications.","authors":"Gwen M Keulen, Joram Huckriede, Kanin Wichapong, Gerry A F Nicolaes","doi":"10.1097/MOH.0000000000000827","DOIUrl":"10.1097/MOH.0000000000000827","url":null,"abstract":"Purpose of review: Thromboembolic complications are a major contributor to global mortality. The relationship between inflammation and coagulation pathways has become an emerging research topic where the role of the innate immune response, and specifically neutrophils in \"immunothrombosis\" are receiving much attention. This review aims to dissect the intricate interplay between histones (from neutrophils or cellular damage) and the haemostatic pathway, and to explore mechanisms that may counteract the potentially procoagulant effects of those histones that have escaped their nuclear localization.Recent findings: Extracellular histones exert procoagulant effects via endothelial damage, platelet activation, and direct interaction with coagulation proteins. Neutralization of histone activities can be achieved by complexation with physiological molecules, through pharmacological compounds, or via proteolytic degradation. Details of neutralization of extracellular histones are still being studied.Summary: Leveraging the understanding of extracellular histone neutralization will pave the way for development of novel pharmacological interventions to treat and prevent complications, including thromboembolism, in patients in whom extracellular histones contribute to their overall clinical status.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"31 5","pages":"230-237"},"PeriodicalIF":3.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861736","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}

引用次数: 0

Shedding light on GPIbα shedding. 揭示 GPIbα 的脱落。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-09-01 Epub Date: 2024-05-09 DOI: 10.1097/MOH.0000000000000826

Caitlin Debaene, Hendrik B Feys, Katrijn R Six

{"title":"Shedding light on GPIbα shedding.","authors":"Caitlin Debaene, Hendrik B Feys, Katrijn R Six","doi":"10.1097/MOH.0000000000000826","DOIUrl":"10.1097/MOH.0000000000000826","url":null,"abstract":"Purpose of review: Ectodomain shedding has been investigated since the late 1980s. The abundant and platelet specific GPIbα receptor is cleaved by ADAM17 resulting in the release of its ectodomain called glycocalicin. This review will address the role of glycocalicin as an end-stage marker of platelet turnover and storage lesion and will consider a potential function as effector in processes beyond hemostasis.Recent findings: Glycocalicin has been described as a marker for platelet senescence, turnover and storage lesion but is not routinely used in a clinical setting because its diagnostic value is nondiscriminatory. Inhibition of glycocalicin shedding improves posttransfusion recovery but little is known (yet) about potential hemostatic improvements. In physiological settings, GPIbα shedding is restricted to the intracellular GPIbα receptor subpopulation suggesting a role for shedding or glycocalicin beyond hemostasis.Summary: So far, all evidence represents glycocalicin as an end-stage biomarker of platelet senescence and a potential trigger for platelet clearance. The extensive list of interaction partners of GPIbα in fields beyond hemostasis opens new possibilities to investigate specific effector functions of glycocalicin.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"224-229"},"PeriodicalIF":3.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140905052","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}

引用次数: 0

Protease activated receptor-4: ready to be part of the antithrombosis spectrum. 蛋白酶激活受体-4：准备好成为抗血栓形成的一部分。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-09-01 Epub Date: 2024-05-29 DOI: 10.1097/MOH.0000000000000828

Izabella Andrianova, Mia Kowalczyk, Frederik Denorme

{"title":"Protease activated receptor-4: ready to be part of the antithrombosis spectrum.","authors":"Izabella Andrianova, Mia Kowalczyk, Frederik Denorme","doi":"10.1097/MOH.0000000000000828","DOIUrl":"10.1097/MOH.0000000000000828","url":null,"abstract":"Purpose of review: Cardiovascular disease is a major cause of death worldwide. Platelets play a key role in this pathological process. The serine protease thrombin is a critical regulator of platelet reactivity through protease activated receptors-1 (PAR1) and PAR4. Since targeting PAR4 comes with a low chance for bleeding, strategies blocking PAR4 function have great antithrombotic potential. Here, we reviewed the literature on platelet PAR4 with a particular focus on its role in thromboinflammation.Recent findings: Functional PAR4 variants are associated with reduced venous thrombosis risk (rs2227376) and increased risk for ischemic stroke (rs773902). Recent advances have allowed for the creation of humanized mouse lines in which human PAR4 is express instead of murine PAR4. This has led to a better understanding of the discrepancies between human and murine PAR4. It also made it possible to introduce single nucleotide polymorphisms (SNPs) in mice allowing to directly test the in vivo functional effects of a specific SNP and to develop in vivo models to study mechanistic and pharmacologic alterations induced by a SNP.Summary: PAR4 plays an important role in cardiovascular diseases including stroke, myocardial infarction and atherosclerosis. Targeting PAR4 hold great potential as a safe antithrombotic strategy.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"238-244"},"PeriodicalIF":3.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180488","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}

引用次数: 0

Platelet lipidomics and de novo lipogenesis: impact on health and disease. 血小板脂质组学和新脂肪生成：对健康和疾病的影响。

IF 3.1 3区医学

Current Opinion in Hematology Pub Date : 2024-09-01 Epub Date: 2024-05-07 DOI: 10.1097/MOH.0000000000000820

Laurence Pirotton, Emma de Cartier d'Yves, Luc Bertrand, Christophe Beauloye, Sandrine Horman

{"title":"Platelet lipidomics and de novo lipogenesis: impact on health and disease.","authors":"Laurence Pirotton, Emma de Cartier d'Yves, Luc Bertrand, Christophe Beauloye, Sandrine Horman","doi":"10.1097/MOH.0000000000000820","DOIUrl":"10.1097/MOH.0000000000000820","url":null,"abstract":"Purpose of review: Lipids play vital roles in platelet structure, signaling, and metabolism. In addition to capturing exogenous lipids, platelets possess the capacity for de novo lipogenesis, regulated by acetyl-coA carboxylase 1 (ACC1). This review aims to cover the critical roles of platelet de novo lipogenesis and lipidome in platelet production, function, and diseases.Recent findings: Upon platelet activation, approximately 20% of the platelet lipidome undergoes significant modifications, primarily affecting arachidonic acid-containing species. Multiple studies emphasize the impact of de novo lipogenesis, with ACC1 as key player, on platelet functions. Mouse models suggest the importance of the AMPK-ACC1 axis in regulating platelet membrane arachidonic acid content, associated with TXA 2 secretion, and thrombus formation. In human platelets, ACC1 inhibition leads to reduced platelet reactivity. Remodeling of the platelet lipidome, alongside with de novo lipogenesis, is also crucial for platelet biogenesis. Disruptions in the platelet lipidome are observed in various pathological conditions, including cardiovascular and inflammatory diseases, with associations between these alterations and shifts in platelet reactivity highlighted.Summary: The platelet lipidome, partially regulated by ACC-driven de novo lipogenesis, is indispensable for platelet production and function. It is implicated in various pathological conditions involving platelets.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"217-223"},"PeriodicalIF":3.1,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900450","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}

引用次数: 0

Splenic filtration of red blood cells in physiology, malaria and sickle cell disease. 生理学、疟疾和镰状细胞病中红细胞的脾过滤。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-08-27 DOI: 10.1097/moh.0000000000000839

Abdoulaye Sissoko,Yosra Ben Othmene,Pierre Buffet

{"title":"Splenic filtration of red blood cells in physiology, malaria and sickle cell disease.","authors":"Abdoulaye Sissoko,Yosra Ben Othmene,Pierre Buffet","doi":"10.1097/moh.0000000000000839","DOIUrl":"https://doi.org/10.1097/moh.0000000000000839","url":null,"abstract":"PURPOSE OF REVIEWThe human spleen clears the blood from circulating microorganisms and red blood cells (RBCs) displaying alterations. This review analyzes how generic mechanisms by which the spleen senses RBC, such pitting, trapping and erythrophagocytosis, impact the pathogenesis of twos major spleen-related diseases, malaria and sickle cell disease (SCD).RECENT FINDINGSScintigraphy, functional histology, comparison of circulating and splenic RBC, ex-vivo perfusion of human spleens and in-silico modeling enable relevant exploration of how the spleen retains and processes RBC in health and disease. Iterative cross-validations between medical observations, in-vitro experiments and in-silico modeling point to mechanical sensing of RBC as a central event in both conditions. Spleen congestion is a common pathogenic process explaining anemia and splenomegaly, the latter carrying a risk of severe complications such as acute splenic sequestration crisis and hypersplenism in SCD. Sickling of hemoglobin S-containing RBC may contribute but not trigger these complications.SUMMARYOngoing progress in the exploration and understanding of spleen-related complications in malaria and SCD open the way to optimized prognosis evaluation and therapeutic applications.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"50 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142224342","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}

引用次数: 0

Tissue factor pathway inhibitor - cofactor-dependent regulation of the initiation of coagulation. 组织因子通路抑制剂--依赖于辅因子的凝血启动调控。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-08-27 DOI: 10.1097/moh.0000000000000838

Josefin Ahnström,Anastasis Petri,James Tb Crawley

{"title":"Tissue factor pathway inhibitor - cofactor-dependent regulation of the initiation of coagulation.","authors":"Josefin Ahnström,Anastasis Petri,James Tb Crawley","doi":"10.1097/moh.0000000000000838","DOIUrl":"https://doi.org/10.1097/moh.0000000000000838","url":null,"abstract":"PURPOSE OF REVIEWIn humans, tissue factor pathway inhibitor (TFPI) exists in two alternatively spliced isoforms, TFPIα and TFPIβ. TFPIα consists of three Kunitz domains (K1, K2 and K3) and a highly basic C-terminal tail. K1 inhibits the tissue factor-activated factor VII complex, K2 specifically inhibits activated factor X, K3 is essential for interaction with its cofactor, protein S, and the basic C-terminus is binds factor V-short (FV-short) with high affinity. TFPIβ consists of K1 and K2 that is glycosylphosphatidylinositol anchored directly to cell surfaces. This review explores the structure/function of TFPI and its cofactors (protein S and FV-short), and the relative contributions that different TFPI isoforms may play in haemostatic control.RECENT FINDINGSRecent data have underscored the importance of TFPIα function and its reliance on its cofactors, protein S and FV-short, in influencing haemostatic control as well as bleeding and thrombotic risk.SUMMARYTFPIα is likely the most important pool of TFPI in modifying the risk of thrombosis and bleeding. TFPIα forms a trimolecular complex with FV-short and protein S in plasma. FV-short expression levels control the circulating levels of TFPIα, whereas protein S exerts essential cofactor mediated augmentation of it anticoagulant function.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":"33 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142185424","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}

引用次数: 0

The role of hematopoiesis in bone repair: an update. 造血在骨修复中的作用：最新进展。

IF 3.2 3区医学

Current Opinion in Hematology Pub Date : 2024-07-01 Epub Date: 2024-05-01 DOI: 10.1097/MOH.0000000000000821

Elise C Jeffery

{"title":"The role of hematopoiesis in bone repair: an update.","authors":"Elise C Jeffery","doi":"10.1097/MOH.0000000000000821","DOIUrl":"10.1097/MOH.0000000000000821","url":null,"abstract":"Purpose of review: The repair of bone after injury requires the participation of many different immune cell populations, which are derived from the hematopoietic lineage. The field of osteoimmunology, or the study of the interactions between bone and the immune system, is a growing field with emerging impact on both the basic science and clinical aspects of fracture healing.Recent findings: Despite previous focus on the innate immune system in fracture healing, recent studies have revealed an important role for the adaptive immune system in bone repair. The composition of adaptive and innate immune cell populations present at the fracture site is significantly altered during aging and diet-induced obesity, which may contribute to delayed healing. Recent data also suggest a complicated relationship between fracture repair and systemic inflammation, raising the possibility that immune populations from distant sites such as the gut can impact the bone repair process.Summary: These findings have important implications for the treatment of fracture patients with antibiotics or anti-inflammatory drugs. Furthermore, the effects of systemic inflammation on fracture repair in the contexts of aging or obesity should be carefully interpreted, as they may not be uniformly detrimental.","PeriodicalId":55196,"journal":{"name":"Current Opinion in Hematology","volume":" ","pages":"163-167"},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900452","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}

引用次数: 0