{"title":"50 years of apheresis for homozygous familial hypercholesterolemia.","authors":"Gilbert R Thompson, Jaimini Cegla","doi":"10.1038/s44161-026-00805-7","DOIUrl":"https://doi.org/10.1038/s44161-026-00805-7","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":10.8,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719020","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}
Zhuoming Zhou, Wei Chen, Haojie Yu, Ira Tabas, Roger SY Foo, Wei Tao
{"title":"mRNA medicine for cardiovascular disease","authors":"Zhuoming Zhou, Wei Chen, Haojie Yu, Ira Tabas, Roger SY Foo, Wei Tao","doi":"10.1038/s44161-026-00804-8","DOIUrl":"10.1038/s44161-026-00804-8","url":null,"abstract":"Cardiovascular disease (CVD) remains the leading cause of global mortality, prompting urgent efforts to explore novel therapeutic approaches. The remarkable success of mRNA technology brings new possibilities for CVD treatment, with numerous preclinical studies establishing proof-of-concept, and several have advanced into clinical trials. Leveraging cumulative experience in mRNA therapeutics, improved understanding of cardiovascular pathophysiology and developments in nanotechnology, genome editing and RNA synthetic biology, mRNA medicine presents promising opportunities for addressing CVDs. Here, we provide an overview of the advancements of mRNA-based biotechnologies for CVDs, including mRNA modifications, mRNA delivery platforms, mRNA-encoded genomic and epigenomic editing, and mRNA-based chimeric antigen receptors for immune cell engineering. We also summarize preclinical and clinical applications of mRNA medicine in various CVDs, including hypercholesterolemia, atherosclerosis, ischemic cardiac injury, cardiac fibrosis and cardiac amyloidosis. Finally, we discuss the challenges and highlight the future directions for bench-to-bedside translation of mRNA technology in the field of CVDs. Zhou et al. review recent technological advances in mRNA-based biotechnologies for cardiovascular disease, examining preclinical applications, clinical trial outcomes, and the key challenges and future directions of these approaches.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 4","pages":"291-307"},"PeriodicalIF":10.8,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693738","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}
{"title":"A wave of fetal hematopoiesis stemming from the hemogenic endothelium of vitelline and umbilical arteries","authors":"","doi":"10.1038/s44161-026-00797-4","DOIUrl":"10.1038/s44161-026-00797-4","url":null,"abstract":"How fetal and adult hematopoietic programs are organized in the embryo has remained a long-standing question. Using lineage tracing in mice, we identified a subset of specialized fetal blood progenitors that originate from the hemogenic endothelium of the embryonic vitelline and umbilical arteries. These fetal hematopoietic cells underlie a previously unrecognized developmental wave of hematopoiesis.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 4","pages":"289-290"},"PeriodicalIF":10.8,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640767","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}
Cristiana Barone, Giulia Quattrini, Alessandro Muratore, Giorgio Anselmi, Yurim Park, Naeema T. Mehmood, Elena Morganti, Roberto Orsenigo, Filipa Timóteo-Ferreira, Anna Cazzola, Arianna Patelli, Thea Milanesi, Bianca Nesti, Francisca Soares-da-Silva, Matthew Nicholls, Gloria Zambelli, Mario Mauri, Silvia Bombelli, Sofia De Marco, Deborah D’Aliberti, Silvia Spinelli, Veronica Bonalume, Alison Domingues, Mahdieh Naghavi Alhosseini, Gianluca Sala, Arianna Colonna, Elisabetta D’Errico, Cristina D’Orlando, Cristina Bianchi, Roberto A. Perego, Raffaella Meneveri, Ana Cumano, Silvia Brunelli, Marella F. T. R. De Bruijn, Andrea Ditadi, Alessandro Fantin, Rocco Piazza, Emanuele Azzoni
{"title":"Fetal-restricted hematopoietic progenitors arise from hemogenic endothelium in vitelline and umbilical arteries","authors":"Cristiana Barone, Giulia Quattrini, Alessandro Muratore, Giorgio Anselmi, Yurim Park, Naeema T. Mehmood, Elena Morganti, Roberto Orsenigo, Filipa Timóteo-Ferreira, Anna Cazzola, Arianna Patelli, Thea Milanesi, Bianca Nesti, Francisca Soares-da-Silva, Matthew Nicholls, Gloria Zambelli, Mario Mauri, Silvia Bombelli, Sofia De Marco, Deborah D’Aliberti, Silvia Spinelli, Veronica Bonalume, Alison Domingues, Mahdieh Naghavi Alhosseini, Gianluca Sala, Arianna Colonna, Elisabetta D’Errico, Cristina D’Orlando, Cristina Bianchi, Roberto A. Perego, Raffaella Meneveri, Ana Cumano, Silvia Brunelli, Marella F. T. R. De Bruijn, Andrea Ditadi, Alessandro Fantin, Rocco Piazza, Emanuele Azzoni","doi":"10.1038/s44161-026-00793-8","DOIUrl":"10.1038/s44161-026-00793-8","url":null,"abstract":"Embryonic hematopoiesis involves successive waves of progenitors from distinct anatomical sites, but the origins and contributions of early hematopoietic stem and progenitor cells (HSPCs) remain incompletely defined. Here we use genetic fate mapping in mice to temporally label hemogenic endothelium (HE) subsets and track their progeny. We show that a wave of fetal-restricted HSPCs arises from HE in the vitelline and umbilical arteries between embryonic days 8.5 and 9.5, preceding the emergence of definitive hematopoietic stem cells. Lineage tracing, single-cell transcriptomic analyses and functional assays revealed that these progenitors are transient and distinct from erythro-myeloid progenitors, contribute extensively to fetal lympho-myelopoiesis but decline postnatally. Our findings reveal a previously unrecognized early HE wave as a key source of fetal-restricted HSPCs, refining the spatial–temporal understanding of layered hematopoiesis and informing developmental origins of blood cell diversity. Barone et al. identify a fetal-restricted wave of hematopoietic progenitors that emerge from the hemogenic endothelium before hematopoietic stem cells and substantially contribute to embryonic lympho-myelopoiesis.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 4","pages":"308-327"},"PeriodicalIF":10.8,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00793-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640788","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}
Jiayin Zhang, Xiaozhi Huang, Zhichao Wu, Jinxiu Liang, Shuo Chen, Chen Xu, Xinjian Wang, Ranran Cao, Xue Ji, Zijian Feng, Tao Lin, Xuyun Li, Xinyang Hu, Wei Zhu, Peidong Han
{"title":"Spastin-mediated severing of glutamylated microtubules controls cardiomyocyte coupling","authors":"Jiayin Zhang, Xiaozhi Huang, Zhichao Wu, Jinxiu Liang, Shuo Chen, Chen Xu, Xinjian Wang, Ranran Cao, Xue Ji, Zijian Feng, Tao Lin, Xuyun Li, Xinyang Hu, Wei Zhu, Peidong Han","doi":"10.1038/s44161-026-00800-y","DOIUrl":"10.1038/s44161-026-00800-y","url":null,"abstract":"Cardiac ischemia–reperfusion injury frequently induces malignant arrhythmias because of connexin 43 (Cx43) mislocalization and impaired cardiomyocyte coupling; yet, effective therapies targeting this mechanism remain scarce. Here we show that ischemic cardiomyopathy in humans and ischemia–reperfusion in mice promote the accumulation and stabilization of glutamylated microtubules, disrupting targeted Cx43 trafficking. This remodeling of the glutamylated microtubule network is mediated by the microtubule-severing enzyme spastin. Spastin overexpression in cardiomyocytes reduced microtubule density, whereas its deficiency caused accumulation of glutamylated, stabilized microtubules. Although cardiomyocyte-specific spastin knockout mice displayed normal cardiac structure and function at baseline, they were highly susceptible to stress-induced malignant arrhythmias. Mechanistically, spastin deficiency impaired microtubule plus end dynamics and Cx43 transport. Notably, genetic or pharmacological reduction of microtubule glutamylation before ischemia–reperfusion preserved Cx43 localization and mitigated oxidative stress-induced injury. Together, these findings identify microtubule glutamylation as a key regulator of cardiac electrical stability and a promising therapeutic target in ischemia–reperfusion injury. Zhang et al. demonstrate that cardiac ischemia–reperfusion injury leads to the accumulation of glutamylated microtubules, which disrupts connexin 43 trafficking and promotes arrhythmias. They further show that targeting microtubule glutamylation or spastin preserves electrical stability and protects the heart from injury.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 4","pages":"366-382"},"PeriodicalIF":10.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635370","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}
Chao Wu, Dantong Li, Sumeet A. Khetarpal, Zixun Yuan, Shengyuan Huang, Justin Ralph Baldovino Guerra, Chunyu Li, Qiulian Zhou, Meixi Quan, Jiaqi He, Meng Wang, Huiying Liang, Anthony Rosenzweig
{"title":"Large-scale identification of protein biomarkers and therapeutic targets in heart and brain disease","authors":"Chao Wu, Dantong Li, Sumeet A. Khetarpal, Zixun Yuan, Shengyuan Huang, Justin Ralph Baldovino Guerra, Chunyu Li, Qiulian Zhou, Meixi Quan, Jiaqi He, Meng Wang, Huiying Liang, Anthony Rosenzweig","doi":"10.1038/s44161-026-00799-2","DOIUrl":"10.1038/s44161-026-00799-2","url":null,"abstract":"Neurological complications frequently impact morbidity, mortality and quality of life in patients with cardiovascular disease, yet the biological mediators connecting cardiovascular and neurological disease are poorly understood. Here we leverage data from 53,014 individuals with plasma proteomic profiles and 50,228 with cardiac and brain magnetic resonance imaging from the UK Biobank to identify circulating proteins correlated with imaging-derived phenotypes (IDPs); 404 and 76 proteins were associated with cardiac or brain IDPs, and 37 with both. Expression analyses suggested these proteins largely originate from fibroblasts, smooth muscle cells, and macrophages in the arterial vasculature. Pathway analyses highlighted cytokine and vasculature-related processes for cardiac IDPs-associated proteins and extracellular matrix pathways in brain IDPs-associated proteins. Mendelian randomization and genetic colocalization supported causal roles for over 63% of these proteins in disease pathogenesis. Over 90% of the proposed candidates have not previously been established as clinical biomarkers or therapeutic targets and represent a catalog for further research. Wu et al. identify circulating proteins associated with cardiovascular and neurological imaging traits and diseases, and validate GDF15 as a shared determinant of heart and brain pathologies in mice.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 4","pages":"351-365"},"PeriodicalIF":10.8,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147610907","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}
{"title":"Cardiovascular PIEZO discovery continues apace to reveal myocardial nerves feeling posture and blood loss","authors":"David J. Beech","doi":"10.1038/s44161-026-00802-w","DOIUrl":"10.1038/s44161-026-00802-w","url":null,"abstract":"The idea of myocardial mechanical reflexes was previously considered, but it struggled to gain traction in mainstream thinking. New research shows PIEZO2 ion channels conferring vagal force sensing in atrial and ventricular myocardium to protect the circulation as blood volume changes with gravity and injury.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 4","pages":"286-288"},"PeriodicalIF":10.8,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147517353","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}