Pub Date : 2024-05-08DOI: 10.1038/s44161-024-00476-2
Gerburg Schwaerzer
{"title":"Alcohol-mediated renal denervation is a safe and efficient treatment for uncontrolled hypertension","authors":"Gerburg Schwaerzer","doi":"10.1038/s44161-024-00476-2","DOIUrl":"10.1038/s44161-024-00476-2","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"493-493"},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140998377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-07DOI: 10.1038/s44161-024-00471-7
Homaira Hamidzada, Simon Pascual-Gil, Qinghua Wu, Gregory M. Kent, Stéphane Massé, Crystal Kantores, Uros Kuzmanov, M. Juliana Gomez-Garcia, Naimeh Rafatian, Renée A. Gorman, Marianne Wauchop, Wenliang Chen, Shira Landau, Tasnia Subha, Michael H. Atkins, Yimu Zhao, Erika Beroncal, Ian Fernandes, Jared Nanthakumar, Shabana Vohra, Erika Y. Wang, Tamilla Valdman Sadikov, Babak Razani, Tracy L. McGaha, Ana C. Andreazza, Anthony Gramolini, Peter H. Backx, Kumaraswamy Nanthakumar, Michael A. Laflamme, Gordon Keller, Milica Radisic, Slava Epelman
Yolk sac macrophages are the first to seed the developing heart; however, owing to a lack of accessible tissue, there is no understanding of their roles in human heart development and function. In this study, we bridge this gap by differentiating human embryonic stem (hES) cells into primitive LYVE1+ macrophages (hESC-macrophages) that stably engraft within contractile cardiac microtissues composed of hESC-cardiomyocytes and fibroblasts. Engraftment induces a human fetal cardiac macrophage gene program enriched in efferocytic pathways. Functionally, hESC-macrophages trigger cardiomyocyte sarcomeric protein maturation, enhance contractile force and improve relaxation kinetics. Mechanistically, hESC-macrophages engage in phosphatidylserine-dependent ingestion of apoptotic cardiomyocyte cargo, which reduces microtissue stress, leading hESC-cardiomyocytes to more closely resemble early human fetal ventricular cardiomyocytes, both transcriptionally and metabolically. Inhibiting hESC-macrophage efferocytosis impairs sarcomeric protein maturation and reduces cardiac microtissue function. Together, macrophage-engineered human cardiac microtissues represent a considerably improved model for human heart development and reveal a major beneficial role for human primitive macrophages in enhancing early cardiac tissue function. Hamidzada et al. show that human pluripotent stem cell–derived macrophages are educated into a tissue-resident fate within human cardiac microtissues, enhancing its function via efferocytic ingestion of stressed cardiomyocyte cargo.
{"title":"Primitive macrophages induce sarcomeric maturation and functional enhancement of developing human cardiac microtissues via efferocytic pathways","authors":"Homaira Hamidzada, Simon Pascual-Gil, Qinghua Wu, Gregory M. Kent, Stéphane Massé, Crystal Kantores, Uros Kuzmanov, M. Juliana Gomez-Garcia, Naimeh Rafatian, Renée A. Gorman, Marianne Wauchop, Wenliang Chen, Shira Landau, Tasnia Subha, Michael H. Atkins, Yimu Zhao, Erika Beroncal, Ian Fernandes, Jared Nanthakumar, Shabana Vohra, Erika Y. Wang, Tamilla Valdman Sadikov, Babak Razani, Tracy L. McGaha, Ana C. Andreazza, Anthony Gramolini, Peter H. Backx, Kumaraswamy Nanthakumar, Michael A. Laflamme, Gordon Keller, Milica Radisic, Slava Epelman","doi":"10.1038/s44161-024-00471-7","DOIUrl":"10.1038/s44161-024-00471-7","url":null,"abstract":"Yolk sac macrophages are the first to seed the developing heart; however, owing to a lack of accessible tissue, there is no understanding of their roles in human heart development and function. In this study, we bridge this gap by differentiating human embryonic stem (hES) cells into primitive LYVE1+ macrophages (hESC-macrophages) that stably engraft within contractile cardiac microtissues composed of hESC-cardiomyocytes and fibroblasts. Engraftment induces a human fetal cardiac macrophage gene program enriched in efferocytic pathways. Functionally, hESC-macrophages trigger cardiomyocyte sarcomeric protein maturation, enhance contractile force and improve relaxation kinetics. Mechanistically, hESC-macrophages engage in phosphatidylserine-dependent ingestion of apoptotic cardiomyocyte cargo, which reduces microtissue stress, leading hESC-cardiomyocytes to more closely resemble early human fetal ventricular cardiomyocytes, both transcriptionally and metabolically. Inhibiting hESC-macrophage efferocytosis impairs sarcomeric protein maturation and reduces cardiac microtissue function. Together, macrophage-engineered human cardiac microtissues represent a considerably improved model for human heart development and reveal a major beneficial role for human primitive macrophages in enhancing early cardiac tissue function. Hamidzada et al. show that human pluripotent stem cell–derived macrophages are educated into a tissue-resident fate within human cardiac microtissues, enhancing its function via efferocytic ingestion of stressed cardiomyocyte cargo.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"567-593"},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141002294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1038/s44161-024-00477-1
Andrea Tavosanis
{"title":"Female sex is not a component of stroke risk in atrial fibrillation","authors":"Andrea Tavosanis","doi":"10.1038/s44161-024-00477-1","DOIUrl":"10.1038/s44161-024-00477-1","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"494-494"},"PeriodicalIF":0.0,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141016723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01DOI: 10.1038/s44161-024-00463-7
Tyler L. Stevens, Henry M. Cohen, Joanne F. Garbincius, John W. Elrod
The mitochondrial calcium (mCa2+) uniporter channel (mtCU) resides at the inner mitochondrial membrane and is required for Ca2+ to enter the mitochondrial matrix. The mtCU is essential for cellular function, as mCa2+ regulates metabolism, bioenergetics, signaling pathways and cell death. mCa2+ uptake is primarily regulated by the MICU family (MICU1, MICU2, MICU3), EF-hand-containing Ca2+-sensing proteins, which respond to cytosolic Ca2+ concentrations to modulate mtCU activity. Considering that mitochondrial function and Ca2+ signaling are ubiquitously disrupted in cardiovascular disease, mtCU function has been a hot area of investigation for the last decade. Here we provide an in-depth review of MICU-mediated regulation of mtCU structure and function, as well as potential mtCU-independent functions of these proteins. We detail their role in cardiac physiology and cardiovascular disease by highlighting the phenotypes of different mutant animal models, with an emphasis on therapeutic potential and targets of interest in this pathway. Stevens et al. review the current knowledge on the regulation of the mitochondrial calcium uniporter channel (mtCU) in cardiac physiology and disease.
{"title":"Mitochondrial calcium uniporter channel gatekeeping in cardiovascular disease","authors":"Tyler L. Stevens, Henry M. Cohen, Joanne F. Garbincius, John W. Elrod","doi":"10.1038/s44161-024-00463-7","DOIUrl":"10.1038/s44161-024-00463-7","url":null,"abstract":"The mitochondrial calcium (mCa2+) uniporter channel (mtCU) resides at the inner mitochondrial membrane and is required for Ca2+ to enter the mitochondrial matrix. The mtCU is essential for cellular function, as mCa2+ regulates metabolism, bioenergetics, signaling pathways and cell death. mCa2+ uptake is primarily regulated by the MICU family (MICU1, MICU2, MICU3), EF-hand-containing Ca2+-sensing proteins, which respond to cytosolic Ca2+ concentrations to modulate mtCU activity. Considering that mitochondrial function and Ca2+ signaling are ubiquitously disrupted in cardiovascular disease, mtCU function has been a hot area of investigation for the last decade. Here we provide an in-depth review of MICU-mediated regulation of mtCU structure and function, as well as potential mtCU-independent functions of these proteins. We detail their role in cardiac physiology and cardiovascular disease by highlighting the phenotypes of different mutant animal models, with an emphasis on therapeutic potential and targets of interest in this pathway. Stevens et al. review the current knowledge on the regulation of the mitochondrial calcium uniporter channel (mtCU) in cardiac physiology and disease.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"500-514"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141049151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-30DOI: 10.1038/s44161-024-00466-4
By dissecting the cell composition and function of arterial grafts derived from the internal thoracic, radial and right gastroepiploic arteries, we identified factors that might promote patency rates of arterial grafts, including combating lipid deposition, disturbances in wall shear stress, smooth muscle cell proliferation, fibrosis and spasm.
{"title":"Directions for promoting patency of arterial grafts","authors":"","doi":"10.1038/s44161-024-00466-4","DOIUrl":"10.1038/s44161-024-00466-4","url":null,"abstract":"By dissecting the cell composition and function of arterial grafts derived from the internal thoracic, radial and right gastroepiploic arteries, we identified factors that might promote patency rates of arterial grafts, including combating lipid deposition, disturbances in wall shear stress, smooth muscle cell proliferation, fibrosis and spasm.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"498-499"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-25DOI: 10.1038/s44161-024-00464-6
Zhan Hu, Min Dai, Yuan Chang, Xiumeng Hua, Ningning Zhang, Xiao Chen, Yixuan Sheng, Zhenyu Xu, Hang Zhang, Yu Zhang, Hao Cui, Hao Jia, Xiu-Jie Wang, Jiangping Song
Common arterial grafts used in coronary artery bypass grafting include internal thoracic artery (ITA), radial artery (RA) and right gastroepiploic artery (RGA) grafts; of these, the ITA has the best clinical outcome. Here, by analyzing the single-cell transcriptome of different arterial grafts, we suggest optimization strategies for the RA and RGA based on the ITA as a reference. Compared with the ITA, the RA had more lipid-handling-related CD36+ endothelial cells. Vascular smooth muscle cells from the RGA were more susceptible to spasm, followed by those from the RA; comparison with the ITA suggested that potassium channel openers may counteract vasospasm. Fibroblasts from the RA and RGA highly expressed GDF10 and CREB5, respectively; both GDF10 and CREB5 are associated with extracellular matrix deposition. Cell–cell communication analysis revealed high levels of macrophage migration inhibitory factor signaling in the RA. Administration of macrophage migration inhibitory factor inhibitor to mice with partial carotid artery ligation blocked neointimal hyperplasia induced by disturbed flow. Modulation of identified targets may have protective effects on arterial grafts. Based on comparative single-cell transcriptomics of arterial grafts deriving from internal thoracic, radial and right gastroepiploic arteries, Hu, Dai, Chang, et al. identify factors that might prevent extracellular matrix deposition and fibrosis and improve the outcomes of coronary artery bypass grafting.
冠状动脉旁路移植术中常用的动脉移植物包括胸内动脉（ITA）、桡动脉（RA）和右胃网膜动脉（RGA）移植物；其中，ITA 的临床效果最好。在此，通过分析不同动脉移植物的单细胞转录组，我们以 ITA 为参考，提出了 RA 和 RGA 的优化策略。与 ITA 相比，RA 有更多与脂质处理相关的 CD36+ 内皮细胞。RGA的血管平滑肌细胞更容易受到痉挛的影响，其次是RA的血管平滑肌细胞；与ITA的比较表明，钾通道开放剂可能会对抗血管痉挛。RA和RGA的成纤维细胞分别高表达GDF10和CREB5；GDF10和CREB5都与细胞外基质沉积有关。细胞-细胞通讯分析显示，RA的巨噬细胞迁移抑制因子信号水平较高。给部分颈动脉结扎的小鼠注射巨噬细胞迁移抑制因子抑制剂可阻断血流紊乱诱导的新内膜增生。调节已确定的靶点可能会对动脉移植物产生保护作用。基于胸内动脉、桡动脉和右胃底动脉移植物的单细胞转录组学比较，Hu、Dai、Chang 等人发现了可防止细胞外基质沉积和纤维化并改善冠状动脉旁路移植术效果的因素。
{"title":"Strategies for arterial graft optimization at the single-cell level","authors":"Zhan Hu, Min Dai, Yuan Chang, Xiumeng Hua, Ningning Zhang, Xiao Chen, Yixuan Sheng, Zhenyu Xu, Hang Zhang, Yu Zhang, Hao Cui, Hao Jia, Xiu-Jie Wang, Jiangping Song","doi":"10.1038/s44161-024-00464-6","DOIUrl":"10.1038/s44161-024-00464-6","url":null,"abstract":"Common arterial grafts used in coronary artery bypass grafting include internal thoracic artery (ITA), radial artery (RA) and right gastroepiploic artery (RGA) grafts; of these, the ITA has the best clinical outcome. Here, by analyzing the single-cell transcriptome of different arterial grafts, we suggest optimization strategies for the RA and RGA based on the ITA as a reference. Compared with the ITA, the RA had more lipid-handling-related CD36+ endothelial cells. Vascular smooth muscle cells from the RGA were more susceptible to spasm, followed by those from the RA; comparison with the ITA suggested that potassium channel openers may counteract vasospasm. Fibroblasts from the RA and RGA highly expressed GDF10 and CREB5, respectively; both GDF10 and CREB5 are associated with extracellular matrix deposition. Cell–cell communication analysis revealed high levels of macrophage migration inhibitory factor signaling in the RA. Administration of macrophage migration inhibitory factor inhibitor to mice with partial carotid artery ligation blocked neointimal hyperplasia induced by disturbed flow. Modulation of identified targets may have protective effects on arterial grafts. Based on comparative single-cell transcriptomics of arterial grafts deriving from internal thoracic, radial and right gastroepiploic arteries, Hu, Dai, Chang, et al. identify factors that might prevent extracellular matrix deposition and fibrosis and improve the outcomes of coronary artery bypass grafting.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"541-557"},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140656620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24DOI: 10.1038/s44161-024-00465-5
The mechanisms by which stroke and myocardial infarction trigger lymphocyte loss remain poorly defined. This study shows that the release of neutrophil extracellular traps (NETs) after stroke and myocardial infarction triggers B cell apoptosis and reduces the number of IgA-producing plasma cells. Therapeutic targeting of NETs is immunoprotective in mice and humans.
中风和心肌梗死引发淋巴细胞丢失的机制仍不十分明确。这项研究表明，中风和心肌梗死后中性粒细胞胞外捕获物（NET）的释放会引发 B 细胞凋亡，并减少产生 IgA 的浆细胞数量。针对中性粒细胞胞外捕获物的治疗对小鼠和人类都有免疫保护作用。
{"title":"Neutrophil extracellular traps trigger IgA loss after stroke and myocardial infarction","authors":"","doi":"10.1038/s44161-024-00465-5","DOIUrl":"10.1038/s44161-024-00465-5","url":null,"abstract":"The mechanisms by which stroke and myocardial infarction trigger lymphocyte loss remain poorly defined. This study shows that the release of neutrophil extracellular traps (NETs) after stroke and myocardial infarction triggers B cell apoptosis and reduces the number of IgA-producing plasma cells. Therapeutic targeting of NETs is immunoprotective in mice and humans.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"496-497"},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140659732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-23DOI: 10.1038/s44161-024-00462-8
Ali A. Tuz, Susmita Ghosh, Laura Karsch, Dimitris Ttoouli, Sai P. Sata, Özgür Ulusoy, Andreas Kraus, Nils Hoerenbaum, Jan-Niklas Wolf, Sabrina Lohmann, Franziska Zwirnlein, Viola Kaygusuz, Vivian Lakovic, Hannah-Lea Tummes, Alexander Beer, Markus Gallert, Stephanie Thiebes, Altea Qefalia, Zülal Cibir, Medina Antler, Sebastian Korste, Elias Haj Yehia, Lars Michel, Tienush Rassaf, Britta Kaltwasser, Hossam Abdelrahman, Ayan Mohamud Yusuf, Chen Wang, Dongpei Yin, Lars Haeusler, Smiths Lueong, Mathis Richter, Daniel R. Engel, Martin Stenzel, Oliver Soehnlein, Benedikt Frank, Mialitiana Solo-Nomenjanahary, Benoît Ho-Tin-Noé, Jens T. Siveke, Matthias Totzeck, Daniel Hoffmann, Anika Grüneboom, Nina Hagemann, Anja Hasenberg, Jean-Philippe Desilles, Mikael Mazighi, Albert Sickmann, Jianxu Chen, Dirk M. Hermann, Matthias Gunzer, Vikramjeet Singh
Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer’s patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3–10 d after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients. Tuz et al. report that stroke and myocardial infarction induce the release of neutrophil extracellular traps (NETs), triggering the loss of B cells and a decrease in immunoglobulin A secretion, and that inhibition of NETs prevents the loss of immunoglobulin A in mice and in patients with stroke.
损伤后体液免疫功能失调是感染和心血管疾病治疗效果不佳的原因。在免疫球蛋白（Ig）中，IgA 是最丰富的粘膜抗体，由肠 Peyer's 斑块（PP）和固有层中的浆 B 细胞产生。我们在这里发现，中风和心肌缺血（MI）患者血液中的 IgA 水平严重下降。在实验小鼠模型中，血浆和粪便中 IgA 的减少伴随着 PP 和固有膜中产生 IgA 的浆细胞的快速丢失。患者和实验小鼠在损伤后 3-10 天可检测到血浆 IgG 减少。中风/脑梗死会引发中性粒细胞胞外捕获器（NET）的释放。中性粒细胞的消耗、NET 的降解或 NET 释放的阻断抑制了实验性中风和心肌梗死以及中风患者 IgA+ 细胞和循环 IgA 的丢失。我们的研究结果揭示了组织损伤触发的全身性 NET 释放如何破坏生理性 Ig 分泌，以及如何在患者体内抑制这种释放。Tuz等人报告说，中风和心肌梗塞会诱导中性粒细胞胞外捕获物（NET）的释放，引发B细胞的丢失和免疫球蛋白A分泌的减少，而抑制NET可防止小鼠和中风患者免疫球蛋白A的丢失。
{"title":"Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion","authors":"Ali A. Tuz, Susmita Ghosh, Laura Karsch, Dimitris Ttoouli, Sai P. Sata, Özgür Ulusoy, Andreas Kraus, Nils Hoerenbaum, Jan-Niklas Wolf, Sabrina Lohmann, Franziska Zwirnlein, Viola Kaygusuz, Vivian Lakovic, Hannah-Lea Tummes, Alexander Beer, Markus Gallert, Stephanie Thiebes, Altea Qefalia, Zülal Cibir, Medina Antler, Sebastian Korste, Elias Haj Yehia, Lars Michel, Tienush Rassaf, Britta Kaltwasser, Hossam Abdelrahman, Ayan Mohamud Yusuf, Chen Wang, Dongpei Yin, Lars Haeusler, Smiths Lueong, Mathis Richter, Daniel R. Engel, Martin Stenzel, Oliver Soehnlein, Benedikt Frank, Mialitiana Solo-Nomenjanahary, Benoît Ho-Tin-Noé, Jens T. Siveke, Matthias Totzeck, Daniel Hoffmann, Anika Grüneboom, Nina Hagemann, Anja Hasenberg, Jean-Philippe Desilles, Mikael Mazighi, Albert Sickmann, Jianxu Chen, Dirk M. Hermann, Matthias Gunzer, Vikramjeet Singh","doi":"10.1038/s44161-024-00462-8","DOIUrl":"10.1038/s44161-024-00462-8","url":null,"abstract":"Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer’s patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3–10 d after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients. Tuz et al. report that stroke and myocardial infarction induce the release of neutrophil extracellular traps (NETs), triggering the loss of B cells and a decrease in immunoglobulin A secretion, and that inhibition of NETs prevents the loss of immunoglobulin A in mice and in patients with stroke.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 5","pages":"525-540"},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00462-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140668782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-10DOI: 10.1038/s44161-024-00467-3
Andrea Tavosanis
{"title":"Pacing of clonal expansion is dictated by its underlying mutation","authors":"Andrea Tavosanis","doi":"10.1038/s44161-024-00467-3","DOIUrl":"10.1038/s44161-024-00467-3","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"3 4","pages":"404-404"},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140606536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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