Pub Date : 2024-03-21DOI: 10.1038/s44161-024-00451-x
Tammy Ryan, Jason D. Roberts
{"title":"Stem cell models of inherited arrhythmias","authors":"Tammy Ryan, Jason D. Roberts","doi":"10.1038/s44161-024-00451-x","DOIUrl":"https://doi.org/10.1038/s44161-024-00451-x","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140222360","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 : 2024-03-15DOI: 10.1038/s44161-024-00445-9
Salli Antila, D. Chilov, H. Nurmi, Zhilin Li, Anni Näsi, Maria Gotkiewicz, Valeriia Sitnikova, Henna Jäntti, Natalia Acosta, H. Koivisto, Jonathan Ray, M. Keuters, Ibrahim Sultan, Flavia Scoyni, Davide Trevisan, Sara Wojciechowski, Mika Kaakinen, Lenka Dvořáková, Abhishek Singh, Jari Jukkola, Nea Korvenlaita, L. Eklund, J. Koistinaho, Sinem Karaman, T. Malm, H. Tanila, Kari Alitalo
{"title":"Sustained meningeal lymphatic vessel atrophy or expansion does not alter Alzheimer’s disease-related amyloid pathology","authors":"Salli Antila, D. Chilov, H. Nurmi, Zhilin Li, Anni Näsi, Maria Gotkiewicz, Valeriia Sitnikova, Henna Jäntti, Natalia Acosta, H. Koivisto, Jonathan Ray, M. Keuters, Ibrahim Sultan, Flavia Scoyni, Davide Trevisan, Sara Wojciechowski, Mika Kaakinen, Lenka Dvořáková, Abhishek Singh, Jari Jukkola, Nea Korvenlaita, L. Eklund, J. Koistinaho, Sinem Karaman, T. Malm, H. Tanila, Kari Alitalo","doi":"10.1038/s44161-024-00445-9","DOIUrl":"https://doi.org/10.1038/s44161-024-00445-9","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140237500","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 : 2024-03-15DOI: 10.1038/s44161-024-00427-x
Monica M. Santisteban, C. Iadecola
{"title":"A deeper dive into amyloid clearance by meningeal lymphatic vessels","authors":"Monica M. Santisteban, C. Iadecola","doi":"10.1038/s44161-024-00427-x","DOIUrl":"https://doi.org/10.1038/s44161-024-00427-x","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140239689","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 : 2024-03-13DOI: 10.1038/s44161-024-00436-w
James T. Brash, Guillermo Diez-Pinel, Chiara Colletto, R. F. Castellan, A. Fantin, C. Ruhrberg
{"title":"The BulkECexplorer compiles endothelial bulk transcriptomes to predict functional versus leaky transcription","authors":"James T. Brash, Guillermo Diez-Pinel, Chiara Colletto, R. F. Castellan, A. Fantin, C. Ruhrberg","doi":"10.1038/s44161-024-00436-w","DOIUrl":"https://doi.org/10.1038/s44161-024-00436-w","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140245730","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 : 2024-03-12DOI: 10.1038/s44161-024-00429-9
Marie Piollet, Florentina Porsch, Giuseppe Rizzo, Frederieke Kapser, Dirk J. J. Schulz, Máté G. Kiss, Kai Schlepckow, Estrella Morenas-Rodriguez, Mustafa Orkun Sen, Julius Gropper, Sourish Reddy Bandi, Sarah Schäfer, Tobias Krammer, Alexander M. Leipold, Matthias Hoke, Mária Ozsvár-Kozma, Hannah Beneš, Martin Schillinger, Erich Minar, Melanie Roesch, Laura Göderle, Anastasiya Hladik, Sylvia Knapp, Marco Colonna, Rudolf Martini, Antoine-Emmanuel Saliba, Christian Haass, Alma Zernecke, Christoph J. Binder, Clément Cochain
Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications—myocardial infarction and stroke—are the leading cause of mortality worldwide1,2. Recent studies have identified triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions3, to be highly expressed in macrophage foam cells in experimental and human atherosclerosis4. However, the role of TREM2 in atherosclerosis is not fully known. Here we show that hematopoietic or global TREM2 deficiency increased, whereas TREM2 agonism decreased, necrotic core formation in early atherosclerosis. We demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages and to the survival of lipid-laden macrophages, indicating a crucial role of TREM2 in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions, thereby controlling plaque necrosis. Piollet, Porsch et al. report that the myeloid receptor TREM2 limits necrotic core formation in atherosclerosis and controls key atherosclerosis-related functions of macrophages, such as efferocytosis, lipid uptake and foam cell survival.
{"title":"TREM2 protects from atherosclerosis by limiting necrotic core formation","authors":"Marie Piollet, Florentina Porsch, Giuseppe Rizzo, Frederieke Kapser, Dirk J. J. Schulz, Máté G. Kiss, Kai Schlepckow, Estrella Morenas-Rodriguez, Mustafa Orkun Sen, Julius Gropper, Sourish Reddy Bandi, Sarah Schäfer, Tobias Krammer, Alexander M. Leipold, Matthias Hoke, Mária Ozsvár-Kozma, Hannah Beneš, Martin Schillinger, Erich Minar, Melanie Roesch, Laura Göderle, Anastasiya Hladik, Sylvia Knapp, Marco Colonna, Rudolf Martini, Antoine-Emmanuel Saliba, Christian Haass, Alma Zernecke, Christoph J. Binder, Clément Cochain","doi":"10.1038/s44161-024-00429-9","DOIUrl":"10.1038/s44161-024-00429-9","url":null,"abstract":"Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications—myocardial infarction and stroke—are the leading cause of mortality worldwide1,2. Recent studies have identified triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions3, to be highly expressed in macrophage foam cells in experimental and human atherosclerosis4. However, the role of TREM2 in atherosclerosis is not fully known. Here we show that hematopoietic or global TREM2 deficiency increased, whereas TREM2 agonism decreased, necrotic core formation in early atherosclerosis. We demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages and to the survival of lipid-laden macrophages, indicating a crucial role of TREM2 in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions, thereby controlling plaque necrosis. Piollet, Porsch et al. report that the myeloid receptor TREM2 limits necrotic core formation in atherosclerosis and controls key atherosclerosis-related functions of macrophages, such as efferocytosis, lipid uptake and foam cell survival.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44161-024-00429-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139304","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 : 2024-03-11DOI: 10.1038/s44161-024-00450-y
Mahmoud Salama Ahmed, Ngoc Uyen Nhi Nguyen, Yuji Nakada, Ching-Cheng Hsu, Ayman Farag, Nicholas T. Lam, Ping Wang, Suwannee Thet, Ivan Menendez-Montes, Waleed M. Elhelaly, Xi Lou, Ilaria Secco, Mateusz Tomczyk, Lorena Zentilin, Jimin Pei, Miao Cui, Matthieu Dos Santos, Xiaoye Liu, Yan Liu, David Zaha, Gregory Walcott, Diana R. Tomchick, Chao Xing, Cheng Cheng Zhang, Nick V. Grishin, Mauro Giacca, Jianyi Zhang, Hesham A. Sadek
Targeting Meis1 and Hoxb13 transcriptional activity could be a viable therapeutic strategy for heart regeneration. In this study, we performd an in silico screening to identify FDA-approved drugs that can inhibit Meis1 and Hoxb13 transcriptional activity based on the resolved crystal structure of Meis1 and Hoxb13 bound to DNA. Paromomycin (Paro) and neomycin (Neo) induced proliferation of neonatal rat ventricular myocytes in vitro and displayed dose-dependent inhibition of Meis1 and Hoxb13 transcriptional activity by luciferase assay and disruption of DNA binding by electromobility shift assay. X-ray crystal structure revealed that both Paro and Neo bind to Meis1 near the Hoxb13-interacting domain. Administration of Paro–Neo combination in adult mice and in pigs after cardiac ischemia/reperfusion injury induced cardiomyocyte proliferation, improved left ventricular systolic function and decreased scar formation. Collectively, we identified FDA-approved drugs with therapeutic potential for induction of heart regeneration in mammals. Ahmed, Nguyen et al. show that two FDA-approved antibiotics, paromomycin and neomycin, promote cardiomyocyte proliferation and improve cardiac function after myocardial infarction in mice and pigs by interfering with the cell division inhibiting function of transcription factors Meis1 and Hoxb13.
针对Meis1和Hoxb13的转录活性可能是一种可行的心脏再生治疗策略。在这项研究中，我们根据已解析的与 DNA 结合的 Meis1 和 Hoxb13 晶体结构，进行了一次硅学筛选，以确定可抑制 Meis1 和 Hoxb13 转录活性的 FDA 批准药物。帕罗霉素（Paro）和新霉素（Neo）在体外诱导新生大鼠心室肌细胞增殖，并通过荧光素酶测定法和电迁移测定法显示出剂量依赖性抑制Meis1和Hoxb13转录活性，破坏DNA结合。X射线晶体结构显示，Paro和Neo都能在Hoxb13相互作用结构域附近与Meis1结合。在成年小鼠和猪心脏缺血再灌注损伤后给予 Paro-Neo 组合药物可诱导心肌细胞增殖、改善左心室收缩功能并减少瘢痕形成。总之，我们发现了美国食品与药物管理局批准的具有诱导哺乳动物心脏再生治疗潜力的药物。艾哈迈德-阮等人的研究表明，美国食品药物管理局批准的两种抗生素--副霉素和新霉素--通过干扰转录因子 Meis1 和 Hoxb13 的细胞分裂抑制功能，促进小鼠和猪心肌梗死后心肌细胞增殖并改善心脏功能。
{"title":"Identification of FDA-approved drugs that induce heart regeneration in mammals","authors":"Mahmoud Salama Ahmed, Ngoc Uyen Nhi Nguyen, Yuji Nakada, Ching-Cheng Hsu, Ayman Farag, Nicholas T. Lam, Ping Wang, Suwannee Thet, Ivan Menendez-Montes, Waleed M. Elhelaly, Xi Lou, Ilaria Secco, Mateusz Tomczyk, Lorena Zentilin, Jimin Pei, Miao Cui, Matthieu Dos Santos, Xiaoye Liu, Yan Liu, David Zaha, Gregory Walcott, Diana R. Tomchick, Chao Xing, Cheng Cheng Zhang, Nick V. Grishin, Mauro Giacca, Jianyi Zhang, Hesham A. Sadek","doi":"10.1038/s44161-024-00450-y","DOIUrl":"10.1038/s44161-024-00450-y","url":null,"abstract":"Targeting Meis1 and Hoxb13 transcriptional activity could be a viable therapeutic strategy for heart regeneration. In this study, we performd an in silico screening to identify FDA-approved drugs that can inhibit Meis1 and Hoxb13 transcriptional activity based on the resolved crystal structure of Meis1 and Hoxb13 bound to DNA. Paromomycin (Paro) and neomycin (Neo) induced proliferation of neonatal rat ventricular myocytes in vitro and displayed dose-dependent inhibition of Meis1 and Hoxb13 transcriptional activity by luciferase assay and disruption of DNA binding by electromobility shift assay. X-ray crystal structure revealed that both Paro and Neo bind to Meis1 near the Hoxb13-interacting domain. Administration of Paro–Neo combination in adult mice and in pigs after cardiac ischemia/reperfusion injury induced cardiomyocyte proliferation, improved left ventricular systolic function and decreased scar formation. Collectively, we identified FDA-approved drugs with therapeutic potential for induction of heart regeneration in mammals. Ahmed, Nguyen et al. show that two FDA-approved antibiotics, paromomycin and neomycin, promote cardiomyocyte proliferation and improve cardiac function after myocardial infarction in mice and pigs by interfering with the cell division inhibiting function of transcription factors Meis1 and Hoxb13.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139293","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 : 2024-03-11DOI: 10.1038/s44161-024-00442-y
Fanglin Ma, Xin Huang, Bishuang Cai
Hepatocytes are recognized as having a primary role in production and clearance of apolipoprotein B100-containing lipoproteins. A new study finds that Kupffer cells can respond to the initial atherogenic dyslipidemia and regulate levels of circulating lipoprotein.
{"title":"Linking MASLD to ACVD through Kupffer cells","authors":"Fanglin Ma, Xin Huang, Bishuang Cai","doi":"10.1038/s44161-024-00442-y","DOIUrl":"10.1038/s44161-024-00442-y","url":null,"abstract":"Hepatocytes are recognized as having a primary role in production and clearance of apolipoprotein B100-containing lipoproteins. A new study finds that Kupffer cells can respond to the initial atherogenic dyslipidemia and regulate levels of circulating lipoprotein.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139336","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 : 2024-03-11DOI: 10.1038/s44161-024-00440-0
Susanne Sattler
Although anti-inflammatory drugs have shown promising results in preclinical cardiovascular research, they have yielded little benefit in clinical trials. Before we can expect positive outcomes, we need to find ways of stratifying patients based on their infectious, inflammatory and autoimmune profile, and identify the right time of treatment.
{"title":"Finding the right balance on the challenging path to clinical translation of anti-inflammatory therapies for ischemic heart disease","authors":"Susanne Sattler","doi":"10.1038/s44161-024-00440-0","DOIUrl":"10.1038/s44161-024-00440-0","url":null,"abstract":"Although anti-inflammatory drugs have shown promising results in preclinical cardiovascular research, they have yielded little benefit in clinical trials. Before we can expect positive outcomes, we need to find ways of stratifying patients based on their infectious, inflammatory and autoimmune profile, and identify the right time of treatment.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139307","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 : 2024-03-11DOI: 10.1038/s44161-024-00446-8
Xuejun Yuan, Thomas Braun
Inhibition of MEIS1–HOXB13 activity by the aminoglycosides neomycin and paromomycin facilitates cardiomyocyte proliferation and heart regeneration.
氨基糖苷类新霉素和副霉素抑制 MEIS1-HOXB13 的活性可促进心肌细胞增殖和心脏再生。
{"title":"Toward drug-induced heart regeneration","authors":"Xuejun Yuan, Thomas Braun","doi":"10.1038/s44161-024-00446-8","DOIUrl":"10.1038/s44161-024-00446-8","url":null,"abstract":"Inhibition of MEIS1–HOXB13 activity by the aminoglycosides neomycin and paromomycin facilitates cardiomyocyte proliferation and heart regeneration.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140139299","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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