Nature cardiovascular research最新文献

Tetraspanin-enriched membrane domains regulate vascular leakage by altering membrane cholesterol accessibility to balance antagonistic GTPases. 富四联蛋白的膜结构域通过改变膜胆固醇的可及性来平衡拮抗gtpase，从而调节血管渗漏。

IF 10.8

Nature cardiovascular research Pub Date : 2025-07-29 DOI: 10.1038/s44161-025-00686-2

Yingjun Ding, Junxiong Chen, Songlan Liu, Jennifer M Hays, Xiaowu Gu, Jonathan D Wren, Constantin Georgescu, Darlene N Reuter, Beibei Liu, Furong He, Xuejun Wang, Quan Wei, Jie Wang, Bharathiraja Subramaniyan, Zhiping Wu, Kiran Kodali, Alaina M Reagan, Willard M Freeman, Cindy K Miranti, Anna Csiszar, Zoltan Ungvari, Kamiya Mehla, Matthew S Walters, Michael H Elliott, Junmin Peng, Tomoharu Kanie, James F Papin, Franklin A Hays, Xin A Zhang

{"title":"Tetraspanin-enriched membrane domains regulate vascular leakage by altering membrane cholesterol accessibility to balance antagonistic GTPases.","authors":"Yingjun Ding, Junxiong Chen, Songlan Liu, Jennifer M Hays, Xiaowu Gu, Jonathan D Wren, Constantin Georgescu, Darlene N Reuter, Beibei Liu, Furong He, Xuejun Wang, Quan Wei, Jie Wang, Bharathiraja Subramaniyan, Zhiping Wu, Kiran Kodali, Alaina M Reagan, Willard M Freeman, Cindy K Miranti, Anna Csiszar, Zoltan Ungvari, Kamiya Mehla, Matthew S Walters, Michael H Elliott, Junmin Peng, Tomoharu Kanie, James F Papin, Franklin A Hays, Xin A Zhang","doi":"10.1038/s44161-025-00686-2","DOIUrl":"https://doi.org/10.1038/s44161-025-00686-2","url":null,"abstract":"Tetraspanins affect metastasis, stemness and angiogenesis, but their roles in inflammation remain to be further clarified. Here we show that endothelial ablation of tetraspanin Cd82 markedly reduces vascular inflammation by mitigating endothelial leakage. Mechanistically, by limiting the anchorages of Cdc42 activator FARP1 and RhoA inhibitor Rnd3 to the plasma membrane (PM), CD82 confines Cdc42 but maintains RhoA activity in endothelial cells, to facilitate endothelium activation. These signaling regulatory effects depend on the ability of CD82 to coalesce and retain accessible cholesterol (AC) at the PM, whereas simvastatin overturns CD82 effects by lowering AC. CD82 supports non-vesicular transfer of AC to the PM through oxysterol-binding protein-related proteins (ORPs). Thus, CD82 and AC promote vascular leakage, whereas statin and ORP inhibitor restrain vascular leakage by decreasing AC. These findings reveal an unconventional anti-inflammation role and mechanism for statin and conceptualize tetraspanin-mediated, AC-mediated and cholesterol transfer-mediated balancing of antagonistic GTPase signaling pathways as regulatory mechanisms for vascular leakage.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144746364","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}

引用次数: 0

Bivalent chromatin domains regulate hematopoietic stem and progenitor cell differentiation. 二价染色质结构域调节造血干细胞和祖细胞的分化。

IF 10.8

Nature cardiovascular research Pub Date : 2025-07-29 DOI: 10.1038/s44161-025-00696-0

Andrea Tavosanis

引用次数: 0

Identification of hypertrophic cardiomyopathy on electrocardiographic images with deep learning. 基于深度学习的心电图像肥厚性心肌病识别。

IF 10.8

Nature cardiovascular research Pub Date : 2025-07-22 DOI: 10.1038/s44161-025-00685-3

Veer Sangha, Lovedeep Singh Dhingra, Arya Aminorroaya, Philip M Croon, Nikhil V Sikand, Sounok Sen, Matthew W Martinez, Martin S Maron, Harlan M Krumholz, Folkert W Asselbergs, Evangelos K Oikonomou, Rohan Khera

{"title":"Identification of hypertrophic cardiomyopathy on electrocardiographic images with deep learning.","authors":"Veer Sangha, Lovedeep Singh Dhingra, Arya Aminorroaya, Philip M Croon, Nikhil V Sikand, Sounok Sen, Matthew W Martinez, Martin S Maron, Harlan M Krumholz, Folkert W Asselbergs, Evangelos K Oikonomou, Rohan Khera","doi":"10.1038/s44161-025-00685-3","DOIUrl":"10.1038/s44161-025-00685-3","url":null,"abstract":"Hypertrophic cardiomyopathy (HCM) is frequently underdiagnosed. Although deep learning (DL) models using raw electrocardiographic (ECG) voltage data can enhance detection, their use at the point of care is limited. Here we report the development and validation of a DL model that detects HCM from images of 12-lead ECGs across layouts. The model was developed using 124,553 ECGs from 66,987 individuals at the Yale New Haven Hospital (YNHH), with HCM features determined by concurrent imaging (cardiac magnetic resonance (CMR) or echocardiography). External validation included ECG images from MIMIC-IV, the Amsterdam University Medical Center (AUMC) and the UK Biobank (UKB), where HCM was defined by CMR (YNHH, MIMIC-IV and AUMC) and diagnosis codes (UKB). The model demonstrated robust performance across image formats and sites (areas under the receiver operating characteristic curve (AUROCs): 0.95 internal testing; 0.94 MIMIC-IV; 0.92 AUMC; 0.91 UKB). Discriminative features localized to anterior/lateral leads (V4 and V5) regardless of layout. This approach enables scalable, image-based screening for HCM across clinical settings.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":10.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692650","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}

引用次数: 0

Collecting lymphatics unzip to drain injured lungs. 收集淋巴管打开，排出受伤的肺部。

IF 9.4

Nature cardiovascular research Pub Date : 2025-07-17 DOI: 10.1038/s44161-025-00682-6

Simon J Cleary

引用次数: 0

The thrombin receptor PAR1 orchestrates changes in lymphatic endothelial cell junction morphology to augment lymphatic drainage during lung injury. 凝血酶受体PAR1协调淋巴内皮细胞连接形态的变化，以增加肺损伤时的淋巴引流。

IF 9.4

Nature cardiovascular research Pub Date : 2025-07-17 DOI: 10.1038/s44161-025-00681-7

Chou Chou, Camila Ceballos Paredes, Barbara Summers, Jade Palmer-Johnson, Anjali Trivedi, Aneel Bhagwani, Kasper B Hansen, Anders S Kristensen, Stefka Gyoneva, Sharon A Swanger, Stephen F Traynelis, Hasina Outtz Reed

{"title":"The thrombin receptor PAR1 orchestrates changes in lymphatic endothelial cell junction morphology to augment lymphatic drainage during lung injury.","authors":"Chou Chou, Camila Ceballos Paredes, Barbara Summers, Jade Palmer-Johnson, Anjali Trivedi, Aneel Bhagwani, Kasper B Hansen, Anders S Kristensen, Stefka Gyoneva, Sharon A Swanger, Stephen F Traynelis, Hasina Outtz Reed","doi":"10.1038/s44161-025-00681-7","DOIUrl":"https://doi.org/10.1038/s44161-025-00681-7","url":null,"abstract":"The lung lymphatic vasculature is capable of remarkable increases in lymphatic drainage in settings of inflammation and edema; however, the mechanisms driving this are not clear. Here we show that lung injury transforms the configuration of lung lymphatic endothelial cell junctions from a continuous 'zippered' configuration to a discontinuous and permeable 'button' configuration. Despite similarity to the junctional changes often seen in leaky and dysfunctional blood vessels, we find that the shift to button junctions in the lymphatic vasculature has an opposite effect, resulting in augmented lung lymphatic drainage. Mechanistically, we demonstrate that lung lymphatic button junction formation in models of lung injury is dependent on the thrombin receptor protease-activated receptor 1, a known mediator of blood vessel permeability. These results uncover a previously unknown role for the thrombin receptor protease-activated receptor 1 in the lymphatic vasculature that promotes a similar change in junction morphology as seen in blood vessels, but with a disparate effect on lymphatic function.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":""},"PeriodicalIF":9.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661224","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}

引用次数: 0

Premenstrual disorders and risk of cardiovascular diseases. 经前紊乱和心血管疾病的风险。

IF 9.4

Nature cardiovascular research Pub Date : 2025-07-11 DOI: 10.1038/s44161-025-00684-4

Yihui Yang, Emma Bränn, Jing Zhou, Dang Wei, Jacob Bergstedt, Fang Fang, Unnur A Valdimarsdóttir, Elizabeth Bertone-Johnson, Donghao Lu

引用次数: 0

A tunable gene therapy for heart regeneration. 心脏再生的可调基因疗法。

IF 9.4

Nature cardiovascular research Pub Date : 2025-07-01 DOI: 10.1038/s44161-025-00666-6

Gabriele D'Uva

引用次数: 0

Hemolyzed red blood cells prevent microvascular bleeding in ischemic organs. 溶血红细胞可防止缺血器官的微血管出血。

IF 9.4

Nature cardiovascular research Pub Date : 2025-07-01 DOI: 10.1038/s44161-025-00689-z

Gerburg Schwaerzer

引用次数: 0

Mechanosensitive PIEZO2 channels shape coronary artery development. 机械敏感的PIEZO2通道影响冠状动脉的发育。

IF 9.4

Nature cardiovascular research Pub Date : 2025-07-01 Epub Date: 2025-06-27 DOI: 10.1038/s44161-025-00677-3

Mireia Pampols-Perez, Carina Fürst, Oscar Sánchez-Carranza, Elena Cano, Jonathan Alexis Garcia-Contreras, Lisa Mais, Wenhan Luo, Sandra Raimundo, Eric L Lindberg, Martin Taube, Arnd Heuser, Anje Sporbert, Dagmar Kainmueller, Miguel O Bernabeu, Norbert Hübner, Holger Gerhardt, Gary R Lewin, Annette Hammes

{"title":"Mechanosensitive PIEZO2 channels shape coronary artery development.","authors":"Mireia Pampols-Perez, Carina Fürst, Oscar Sánchez-Carranza, Elena Cano, Jonathan Alexis Garcia-Contreras, Lisa Mais, Wenhan Luo, Sandra Raimundo, Eric L Lindberg, Martin Taube, Arnd Heuser, Anje Sporbert, Dagmar Kainmueller, Miguel O Bernabeu, Norbert Hübner, Holger Gerhardt, Gary R Lewin, Annette Hammes","doi":"10.1038/s44161-025-00677-3","DOIUrl":"10.1038/s44161-025-00677-3","url":null,"abstract":"Coronary arteries develop under constant mechanical stress. However, the role of mechanosensitive ion channels in this process remains poorly understood. Here we show that the ion channel PIEZO2, which responds to mechanical stimuli, is expressed in specific coronary endothelial cell populations during a critical phase of coronary vasculature remodeling. These Piezo2+ coronary endothelial cells show distinct transcriptional profiles and have mechanically activated ionic currents. Strikingly, PIEZO2 loss-of-function mouse embryos and mice with human pathogenic variants of PIEZO2 show abnormal coronary vessel development and cardiac left ventricular hyperplasia. We conclude that an optimal balance of PIEZO2 channel function contributes to proper coronary vessel formation, structural integrity and remodeling, and is likely to support normal cardiac function. Our study highlights the importance of mechanical cues in cardiovascular development and suggests that defects in this mechanosensing pathway may contribute to congenital heart conditions.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":"921-937"},"PeriodicalIF":9.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12259469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512905","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}

引用次数: 0

O-GlcNAcylation promotes angiogenic transdifferentiation to reverse vascular ischemia. o - glcn酰化促进血管生成转分化，逆转血管缺血。

IF 10.8

Nature cardiovascular research Pub Date : 2025-07-01 Epub Date: 2025-07-04 DOI: 10.1038/s44161-025-00673-7

Shuang Li, Alexander J Lu, Eric S Nagueh, Yanqiang Li, Michael Graber, Kaylee N Carter, Elisa Morales, Crystina L Kriss, Kaifu Chen, Junchen Liu, Guangyu Wang, John P Cooke, Li Lai

{"title":"O-GlcNAcylation promotes angiogenic transdifferentiation to reverse vascular ischemia.","authors":"Shuang Li, Alexander J Lu, Eric S Nagueh, Yanqiang Li, Michael Graber, Kaylee N Carter, Elisa Morales, Crystina L Kriss, Kaifu Chen, Junchen Liu, Guangyu Wang, John P Cooke, Li Lai","doi":"10.1038/s44161-025-00673-7","DOIUrl":"10.1038/s44161-025-00673-7","url":null,"abstract":"The restoration of the microvasculature is essential to cardiovascular regeneration. Our previous work demonstrated that angiogenic transdifferentiation of fibroblasts into endothelial cells facilitates vascular recovery following limb ischemia and is accompanied by a metabolic shift toward glycolysis. However, a comprehensive characterization of the metabolic alterations that contribute to the transdifferentiation process is still lacking. Here we identify a marked upregulation of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the substrate for O-GlcNAcylation, during transdifferentiation. Enhancing this pathway promotes, whereas inhibiting it impairs, the efficiency of transdifferentiation. Mechanistically, we demonstrate that O-GlcNAcylation facilitates chromatin remodeling through modification of HIRA, a histone chaperone responsible for de novo deposition of the noncanonical histone variant H3.3, a process intimately linked to transcriptional activation. These findings are further supported by in vivo lineage tracing and conditional knockout mouse models. Collectively, our study demonstrates that O-GlcNAcylation enhances angiogenic transdifferentiation through a metabolic-and-epigenetic-coupled mechanism, thereby strengthening vascular recovery.","PeriodicalId":74245,"journal":{"name":"Nature cardiovascular research","volume":" ","pages":"904-920"},"PeriodicalIF":10.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565497","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}

引用次数: 0