Nature cardiovascular research最新文献

{"title":"A balancing act keeps the brain fed","authors":"Stefan Stamenkovic, Andy Y. Shih","doi":"10.1038/s44161-026-00847-x","DOIUrl":"10.1038/s44161-026-00847-x","url":null,"abstract":"Cerebral hemodynamic dysfunction drives unhealthy brain aging, but the role of capillaries remains unclear. Using spatial transcriptomic and advanced imaging, a study now reveals how pericyte dysfunction disrupts blood-flow distribution, causing deep-brain hypoperfusion despite preserved overall cerebral blood flow.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 8","pages":"670-672"},"PeriodicalIF":12.6,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671440","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":"Pericyte KATP channel hyperactivity redistributes cortical blood flow in a CADASIL mouse model","authors":"Danielle A. Jeffrey, Eric W. Prince, Niloufar Khakpour, Hannah R. Ferris, Colin H. Peters, Gregory Seedorf, Phinea Z. Romero, Mayra Bueno Guerrero, Abigail N. Russell, Katherine Glodoski, Gregory L. Futia, Stephanie K. Bonney, Michael A. Thornton, Emily A. Gibson, Catherine Proenza, Anastacia M. Garcia, Nikolaos M. Tsoukias, Fabrice Dabertrand","doi":"10.1038/s44161-026-00844-0","DOIUrl":"10.1038/s44161-026-00844-0","url":null,"abstract":"Cerebral hemodynamic dysfunction is a key driver of unhealthy brain aging. Impaired microcirculatory reactivity leads to uneven perfusion, rendering deeper brain regions more vulnerable and thereby contributing to cognitive decline. Yet how capillaries contribute to these deficits remains poorly defined. Here we combined spatial transcriptomics with in vivo two-photon and three-photon imaging to measure layer-specific cerebral blood flow in control and small vessel disease model mice (CADASIL TgNotch3R169C). We found downregulation of ATP-synthesizing genes, indicating microvascular metabolic impairment that paralleled impaired pericyte bioenergetics. This energy deficit coincided with diminished tone in the arteriole–capillary transitional zone and reduced deep-layer perfusion. Complementary electrophysiology, ex vivo and in silico approaches, revealed that hyperactive KATP channels in pericytes drive a redistribution of cerebral blood flow toward superficial cortical layers. This loss of spatial perfusion equalization, despite preserved global flow, contributed to deep-layer hypoperfusion, establishing a previously underrecognized but tractable vascular function disrupted in aging pathology. By integrating spatial transcriptomics, advanced in vivo imaging, ex vivo myography, electrophysiology, in vitro functional assays and in silico modeling, Jeffrey et al. delineate a previously unrecognized mechanism of cerebral blood flow dysregulation and highlight the contribution of microvascular compartments to unhealthy brain aging.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 8","pages":"725-743"},"PeriodicalIF":12.6,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00844-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671456","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}

{"title":"Spatiotemporal transcriptomics of human cardiovascular progenitors in pig hearts identifies Midkine as a positive regulator of neovascularization","authors":"Swarnaseetha Adusumalli, Kye Siong Leong, Samantha Lim, Vincent Ren, Li Yen Chong, Clarissa Tan, Roy Tham, Min En Cheng, Lei Ye, Yibin Wang, Enrico Petretto, Lynn Yap","doi":"10.1038/s44161-026-00851-1","DOIUrl":"10.1038/s44161-026-00851-1","url":null,"abstract":"Stem-cell-based cardiac repair holds promise for the infarcted myocardium, yet the in vivo molecular behavior of transplanted cells is poorly understood. Using time series spatial transcriptomics, we profiled human pluripotent stem-cell-derived cardiovascular progenitors engrafted into a pig model. We show that the engrafted cardiovascular progenitors progressively upregulated genes associated with cardiac maturation, oxidative metabolism, calcium handling and fibrosis resolution. Cell–cell communication analysis identified Midkine (MDK), secreted by the human xenograft, as a key regulator of host neovascularization. We validated this using immunohistochemistry, lentiviral MDK overexpression and functional assays that demonstrated enhanced endothelial cell migration and increased CD31+ vascular density in vivo. A publicly available interactive Shiny atlas of spatial and temporal transcriptomic data from myocardial infarction pig hearts with human xenografts is provided. These findings advance mechanistic understanding of stem-cell-mediated cardiac repair and identify MDK as a tractable target for therapeutic angiogenesis in ischemic heart disease. Adusumalli et al. used spatial transcriptomics of human pluripotent stem-cell-derived cardiac progenitor grafts transplanted into pig hearts to identify Midkine as a regulator of neovascularization.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 8","pages":"744-762"},"PeriodicalIF":12.6,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148650002","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":"Utility of high-sensitivity cardiac troponin I normalized to left ventricular mass in detection of stable coronary artery disease","authors":"Sina Fathieh, Michael P. Gray, Owen Tang, Katharine A. Bate, Stephen T. Vernon, Elijah Genetzakis, Soloman Saleh, Gillian Murtagh, Jean Y. Yang, Collin Tran, David R. Sullivan, Paul Bonnitcha, David S. Celermajer, Louise Cullen, Ravinay Bhindi, Jamil Mayet, Stephen J. Nicholls, Stuart M. Grieve, Gemma A. Figtree","doi":"10.1038/s44161-026-00837-z","DOIUrl":"10.1038/s44161-026-00837-z","url":null,"abstract":"Coronary artery disease often develops silently before myocardial infarction, and current risk-based prevention pathways miss some individuals with clinically important disease, particularly those without standard modifiable cardiovascular risk factors. High-sensitivity cardiac troponin I is a blood biomarker of low-level myocardial injury, but its relationship to silent coronary atherosclerosis remains incompletely understood. Here we show, in 1,613 adults undergoing coronary computed tomography (CT) imaging, that low-level high-sensitivity cardiac troponin I is associated with clinically actionable coronary disease, defined by coronary calcium score ≥100, and with quantitative CT markers of plaque burden. A threshold of 2.3 ng l−1 enriched for actionable disease, especially in individuals without standard risk factors. Normalizing troponin for myocardial mass, age and renal function improved prediction and provided mechanistic insight into baseline troponin elevation in chronic coronary syndromes. A two-stage strategy using troponin before CT imaging increased diagnostic yield and reduced the number of scans required. Prospective validation is warranted before clinical implementation. Fathieh et al. investigate the clinical value of a pre-screening strategy based on high-sensitivity troponin levels to identify patients at risk of coronary artery disease and in need of imaging diagnosis, even in the absence of traditional risk factors.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 8","pages":"763-776"},"PeriodicalIF":12.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00837-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633091","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}

{"title":"Severe obesity alters contractile function in heart failure with preserved ejection fraction","authors":"Xiulin Koehler","doi":"10.1038/s44161-026-00858-8","DOIUrl":"10.1038/s44161-026-00858-8","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 8","pages":"667-667"},"PeriodicalIF":12.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148610845","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":"Immature neutrophils sound the alarm in acute myocardial infarction","authors":"Alexander J. F. Thurston, Nicholas L. Mills","doi":"10.1038/s44161-026-00848-w","DOIUrl":"10.1038/s44161-026-00848-w","url":null,"abstract":"Myocardial infarction can cause lasting cardiac damage, heart failure and death, and immune responses are increasingly recognized as key determinants of outcomes. A study now shows that ST-segment elevation myocardial infarction (STEMI) mobilizes immature neutrophil progenitors from the bone marrow, predicting increased mortality risk.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 8","pages":"668-669"},"PeriodicalIF":12.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581451","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":"Cardiac mechanical loading inhibits tumor cell proliferation","authors":"Elisa Martini","doi":"10.1038/s44161-026-00857-9","DOIUrl":"10.1038/s44161-026-00857-9","url":null,"abstract":"","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 8","pages":"665-665"},"PeriodicalIF":12.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148581540","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":"Mavacamten shows broad benefit in human and mouse models of MYBPC3-related hypertrophic cardiomyopathy","authors":"Laura Sen-Martín, Ángel Fernández-Trasancos, Miguel Á. López-Unzu, Agata Bak, Magdalena Zafra-Castellano, Rajiven Srikantharajah, Divya Pathak, Annika Klotz, Michel N. Kuehn, Alessia Ferrarini, Verónica Labrador-Cantarero, David Sánchez-Ortiz, María Rosaria Pricolo, Natalia Vicente, Diana Velázquez-Carreras, Lucía Sánchez-García, Jon Sicilia, José Ángel Nicolás-Ávila, María Sánchez-Díaz, Saskia Schlossarek, Lorena Cussó, Manuel Desco, María Villalba-Orero, Gabriela Guzmán-Martínez, Enrique Calvo, Roberto Barriales-Villa, Jesús Vázquez, Fátima Sánchez-Cabo, Andrés Hidalgo, Pieter P. de Tombe, Lucie Carrier, James A. Spudich, Kathleen M. Ruppel, Florian Weinberger, Olivier Cazorla, Anthony L. Hessel, Jorge Alegre-Cebollada","doi":"10.1038/s44161-026-00833-3","DOIUrl":"10.1038/s44161-026-00833-3","url":null,"abstract":"Mavacamten is a targeted treatment for hypertrophic cardiomyopathy, a disease caused by genetic variants affecting mainly sarcomeric myosin and its regulator cardiac myosin-binding protein C (cMyBP-C, encoded by MYBPC3). Here we generate knock-in mice including missense pathogenic variant cMyBP-C p.R502W, which unlike carriers of cMyBP-C truncations, develop pathogenic myocardial remodeling with preserved cMyBP-C levels and localization. Mechanistically, R502W reduces cMyBP-C–myosin affinity and generates sarcomere hypercontractility due to increased Ca2+ sensitivity and a favored ON structural state of myosin. Even though these pathomechanisms do not overlap with those triggered by truncating MYBPC3 variants, mavacamten blunts myocardial remodeling both in R502W and cMyBP-C-deficient hearts, correlating with the drug’s ability to restore OFF myosin in R502W sarcomeres. In R502W human engineered heart tissues, mavacamten also opposes hypercontractility. Hence, our results indicate that mavacamten is effective in treating hypertrophic cardiomyopathy caused by both truncating and missense MYBPC3 variants regardless of their primary pathomechanisms. Sen-Martín et al. demonstrate that mavacamten exerts therapeutic benefit in hypertrophic cardiomyopathy caused by both missense and truncating MYBPC3 variants by reducing hypercontractility and myocardial remodeling through normalization of myosin activity.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 7","pages":"638-657"},"PeriodicalIF":12.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407236","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":"Territorial heterogeneity of atherosclerosis and vascular calcification","authors":"Luca Saba, Jagat Narula","doi":"10.1038/s44161-026-00832-4","DOIUrl":"10.1038/s44161-026-00832-4","url":null,"abstract":"Atherosclerosis is a systemic disease of the arterial tree that often assumes variable forms across vascular territories. As a result, atherosclerotic plaques in different vascular beds differ in frequency, composition, stability and propensity to rupture. Here, we argue that this territorial variability is a manifestation of partially predictable principles. Embryological origin and developmental programming create regionally distinct smooth muscle cell lineages and extracellular matrix architectures, predisposing vascular segments to characteristic modes of injury and repair. Local hemodynamic processes and vessel structures further influence this architecture, leading to distinct atherosclerotic plaque evolution. Microvascular and macrovascular calcification contribute to these processes by amplifying local signals, including inflammation and environmental cues, and by driving the chondrogenic and osteogenic transformation of vascular cells. By synthesizing evidence on divergent atherosclerotic and calcification patterns across vascular beds, the concept of territory-adapted imaging and therapy may improve prevention and risk stratification. Saba and Narula review the causes and consequences of the heterogeneous manifestations of atherosclerosis across vascular beds and share their perspective on vascular calcification as a readout of the underlying processes, with clinical implications for diagnosis and management.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 7","pages":"597-604"},"PeriodicalIF":12.6,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148407247","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":"Depth of neutrophil mobilization stratifies survival in ST-elevation myocardial infarction","authors":"Mathis Richter, Jessica von Göwels, Maximilian Fähndrich, Christian Lipgens Fernandez, Katharina Grohn, Marius Welzel, Dennis Schwarz, Alexander Lang, Amin Polzin, Sara Reinartz Groba, Luca Farinola, Susmita Ghosh, Jan-Niklas Heming, Hanna Aleth, Anastassia Akhalkatsi, Kian Marjani, Nicole Rübsamen, Tobias Radecke, Frank Rosenbauer, Albert Sickmann, André Karch, Alexander Zarbock, Jens Minnerup, Jürgen Sindermann, Alexander Bender, Jan Rossaint, Steffen Ormanns, Matthias Gunzer, Mariano Malamud, Rainer Kaiser, Kami Pekayvaz, Dominik Heider, Holger Reinecke, Lena Makowski, Christian Jung, Carlos Silvestre-Roig, Malte Kelm, Norbert Gerdes, Raphael Chevre, Stefan A. Lange, Oliver Soehnlein","doi":"10.1038/s44161-026-00836-0","DOIUrl":"10.1038/s44161-026-00836-0","url":null,"abstract":"Systemic inflammatory responses shape clinical outcomes in acute cardiovascular disease. Because of their functional plasticity and rapid turnover, neutrophils have emerged as dynamic indicators of inflammatory stress. Here we profile the appearance of distinct neutrophil maturation stages in patients with ST-elevation myocardial infarction, heart failure and stroke. Our data reveal the mobilization of immature neutrophils in all groups; however, patients with ST-elevation myocardial infarction exhibited the most pronounced engagement of this response, including the appearance of CD16lowCD10neg preneutrophils (preNeus), the final mitotic neutrophil progenitor, which was associated with disease outcome. Plasma cytokine profiling identified a coordinated inflammatory signature associated with preNeu mobilization, consistent with emergency granulopoiesis. PreNeus were identifiable as immature granulocytes in routine blood count analysis, where they predicted 30-day mortality better than established biomarkers in two clinical cohorts. Immature granulocytes also remained independently associated with survival in multivariate models incorporating risk factors, enabling the immediate identification of vulnerable patients with ST-elevation myocardial infarction upon hospital admission. Richter et al. show that the mobilization of neutrophil progenitors assessed from routine blood tests can predict 30-day mortality in patients following ST-elevation myocardial infarction and enable rapid risk stratification.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":"5 8","pages":"693-704"},"PeriodicalIF":12.6,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s44161-026-00836-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148383325","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}