Circulation research最新文献

{"title":"Endothelial NOX1 Drives Obesity via Skeletal Muscle Mitochondrial Dysfunction.","authors":"Kai Huang,Yuanli Huang,Yuhan Zhang,Yixuan Zhang,Nicholas W Hatch,Julie K Freed,Hua Linda Cai","doi":"10.1161/circresaha.125.326768","DOIUrl":"https://doi.org/10.1161/circresaha.125.326768","url":null,"abstract":"BACKGROUNDPresently, we investigated hypothesized roles and mechanisms of cell type-specific, selective activation of different vascular NOX (NADPH oxidase) isoforms in obesity and metabolic syndrome.METHODS AND RESULTSExpression of NOX1 (NOX isoform 1) was significantly upregulated in wild-type mice fed a high-fat diet. Global knockout of NOX1 (NOX1-/y), rather than of NOX2 (NOX isoform 2)/NOX4 (NOX isoform 4), markedly abrogated high-fat feeding-induced body weight/fat mass gain, preadipocyte differentiation, fatty liver, glucose intolerance, and insulin/leptin resistance. Intriguingly, endothelial-specific NOX1 knockout (Cdh5cre-cre-inducible NOX1flox/flox knockout/floxed mice [NOX1CKO]), rather than vascular smooth muscle-specific NOX1 knockout (Myh11cre-NOX1CKO), substantially alleviated obesity and metabolic syndrome. Consistently, endothelial-specific NOX1 knockin mice (Cdh5cre-cre-inducible NOX1flox/flox knockin/floxed) fed a high-fat diet displayed exaggerated metabolic disorders. Endothelial cell-specific knockout/knockin of NOX1 was confirmed using endothelial cell washout experiments. Food/water intakes were not different from corresponding controls in high-fat-fed NOX1-/y, Cdh5cre-NOX1CKO, or Cdh5cre-cre-inducible NOX1flox/flox knockin/floxed mice, indicating no difference in energy intake. Instead, spontaneous activity, exercise capacity, mitochondrial oxygen consumption/ATP production, skeletal muscle mitochondrial function (reactive oxygen species production and swelling activity), and mitochondrial cristae structure were all substantially improved in NOX1-/y or Cdh5cre-NOX1CKO mice, indicating augmented energy expenditure attributed to preserved skeletal muscle mitochondrial function. Supportively, Cdh5cre-cre-inducible NOX1flox/flox knockin/floxed mice displayed deteriorated exercise capacity and skeletal muscle mitochondrial dysfunction. Endothelium-dependent vasorelaxation was restored in high-fat-fed NOX1-/y or Cdh5cre-NOX1CKO mice, confirming improved endothelial function. RNA-sequencing identified 4 genes (Cntnap4 [contactin-associated protein-like 4], Sgsm1, Tll2, and Syt9) and 7 genes (Odf3l2, Col9a1 [collagen type IX alpha 1 chain], Cldn23, Atp5g2, Nkx6-3, Ntsr2, and Zfp69) significantly downregulated/upregulated in high-fat-fed Cdh5cre-NOX1CKO mice, among which Cntnap4 and Col9a1 linked to muscular disorders. Importantly, we observed marked upregulation of NOX1 in isolated coronary arteries from human patients with obesity.CONCLUSIONSTaken together, our data for the first time establish a novel and paradigm-shifting concept that endothelial NOX1 drives systematic metabolic phenotypes, via impairment in skeletal muscle mitochondrial dysfunction with novel genetic signatures. Tissue-specific targeting of endothelial NOX1 and novel candidate genes may prove to be robustly effective in treating obesity and metabolic syndrome.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"25 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery of Mitochondria Attenuates Elastase-Induced Abdominal Aortic Aneurysm in Mice.","authors":"Dunpeng Cai,Ruimei Zhou,Shi-You Chen","doi":"10.1161/circresaha.125.328060","DOIUrl":"https://doi.org/10.1161/circresaha.125.328060","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"17 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise Metabolic Memory Halts Pathological Cardiac Hypertrophy via PDK4.","authors":"Cankun Zheng,Xiaoxia Huang,Xinnan Wei,Changzhu Liang,Lu Chen,Mingjue Li,Rui Zhang,Mingyuan He,Zhihong Li,Rongzhan Lin,Mengjia Shen,Jichen Liu,Qiancheng Wang,Jianhua Huang,Wangjun Liao,Jianping Bin,Hairuo Lin,Yulin Liao","doi":"10.1161/circresaha.125.326889","DOIUrl":"https://doi.org/10.1161/circresaha.125.326889","url":null,"abstract":"BACKGROUNDPathological cardiac hypertrophy remains a major contributor to heart failure, with impaired glucose metabolism playing a central role. Although exercise is known to enhance myocardial glucose utilization, the long-term metabolic reprogramming effects of exercise and their role in preventing pathological hypertrophy are poorly understood. This study elucidates the mechanisms underlying the sustained metabolic memory induced by exercise-induced hypertrophic preconditioning (EHP) and its cardioprotective effects, with a focus on RNA methylation and arachidonic acid metabolism.METHODSWe used positron emission tomography/computed tomography to assess cardiac glucose uptake and bulk RNA sequencing to profile myocardial gene expression in sedentary and EHP mice. Genetic manipulation of Pdk4 (pyruvate dehydrogenase kinase 4) was achieved via adeno-associated virus-mediated overexpression and tamoxifen-inducible, cardiac-specific Pdk4 knockout. Pressure overload was induced by transverse aortic constriction in cardiac-specific Pdk4 knockout and control (MCM [Myh6-MerCreMer]) mice. Epigenetic regulation of Pdk4 by EHP was investigated using pyrosequencing, single-base elongation- and ligation-based quantitative polymerase chain reaction and dual-luciferase assays. Untargeted metabolomics and molecular docking, molecular dynamics simulation, and cellular thermal shift assay were performed on heart tissues and neonatal rat cardiomyocytes/fibroblasts to identify key metabolites and their mechanisms of action.RESULTSEHP conferred sustained myocardial glucose preference even after regression of physiological hypertrophy, mediated through METTL3-dependent m6A RNA methylation that suppressed Pdk4 expression. Pdk4 overexpression abolished EHP-mediated cardioprotection, whereas Pdk4 deletion enhanced cardiac function and attenuated fibrosis under pressure overload. Metabolomic profiling identified arachidonic acid-derived metabolites 5-KETE, 12-keto-leukotriene B4, and 20-hydroxy-leukotriene B4 as novel inhibitors of hypertrophy and fibrosis. These metabolites attenuated cardiomyocyte hypertrophy and fibroblast transdifferentiation through inhibition of the ERK (extracellular signal-regulated kinase) 2/MAPK1 pathway.CONCLUSIONSThis study establishes a unified mechanism by which EHP induces metabolic memory through RNA methylation-dependent suppression of Pdk4, leading to altered arachidonic acid metabolism and the accumulation of protective lipid mediators. These findings highlight the therapeutic potential of targeting the PDK4-arachidonic acid metabolites axis to mitigate pathological cardiac remodeling.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"29 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leptin Receptor Fibroblasts Are Preferential Contributors to Cardiac Fibrosis.","authors":"Veronica Larcher,Ariane Fischer,Lunfeng Zhang,Omar Almolla,Mattia Chiesa,Francesca Andriani,Chiara Wernet,Simone Serio,Lukas Tombor,Sofia Peruzzo,Debanjan Mukherjee,Rossana Bussani,Serena Zacchigna,Ralf H Adams,Stefanie Dimmeler,Sylvia M Evans,Paola Cattaneo,Nuno Guimarães-Camboa","doi":"10.1161/circresaha.125.327701","DOIUrl":"https://doi.org/10.1161/circresaha.125.327701","url":null,"abstract":"BACKGROUNDCardiac fibrosis, a hallmark of heart failure and an unmet clinical need, arises from pathological activation of preexisting cardiac fibroblasts (CFs), but the contribution of CF heterogeneity to this process remains unclear.METHODSMurine models were used to lineage trace or deplete a specific sub-population of CFs at baseline and after myocardial infarction. Transcriptional and epigenetic differences between fibroblast subsets were assessed using next-generation sequencing. Conservation in humans was evaluated through single-cell RNA-seq data sets and histological examination.RESULTSIn mice, fibroblasts were the sole cardiac cell type expressing the signaling-capable isoform of the LepR (leptin receptor). LepR+ CFs emerged neonatally, occupied a defined niche in the coronary adventitia, exhibited enhanced hedgehog signaling, and responded to leptin. After myocardial infarction, LepR-Cre+ CFs proliferated more than interstitial CFs, became a predominant fibroblast lineage in the scar, and their genetic ablation reduced fibrosis while improving function. LepR+ CFs were also detected in the human heart, where they were embedded in an adipocyte-rich niche.CONCLUSIONSThese findings identify adventitial fibroblasts as key drivers of pathological remodeling and demonstrate that fibroblasts, rather than cardiomyocytes, are the principal responders to leptin in the heart, redefining how this major endocrine pathway influences cardiac remodeling and disease.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"56 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147685086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Female-Biased VSMC GRNs Predict MYH9 as Regulator of Fibrous Plaque Phenotype.","authors":"R Noah Perry,Graham Lenert,Ernest Diez Benavente,Aydin Bölük,Rebecca Hernandez,Lijiang Ma,Nicolas Barbera,Kelsey Watts,Victor Mendoza,Tiit Örd,Mari Taipale,Nadja Sachs,Jessica Pauli,Michal Mokry,Dominique P V de Kleijn,Menno P J de Winther,Manuel Mayr,Lars Maegdefessel,Karen Reue,Minna U Kaikkonen,Johan L M Björkegren,Hester M den Ruijter,Mete Civelek","doi":"10.1161/circresaha.125.326941","DOIUrl":"https://doi.org/10.1161/circresaha.125.326941","url":null,"abstract":"BACKGROUNDAtherosclerosis, an inflammatory driver of coronary artery disease, manifests as unstable atheromatous plaques and stable fibrous plaques. Although atheromatous plaques have been extensively studied, fibrous plaques, particularly in females aged <50 years, where erosion contributes significantly to coronary thrombosis, remain less understood. The molecular mechanisms underlying sex differences in plaque biology, including vascular smooth muscle cell contributions, are incompletely defined.METHODSSex-specific gene regulatory networks (GRNs) were constructed from RNA-sequencing data of cultured human vascular smooth muscle cells isolated from 119 male and 32 female heart transplant donors. Network preservation analyses identified female-biased GRNs, which were evaluated in single-cell RNA-sequencing data sets from human carotid atherosclerotic plaques. Bayesian network modeling and proteomic analyses were used to identify and validate regulatory drivers.RESULTSTwo female-biased vascular smooth muscle cell networks, GRNfloralwhite and GRNyellowgreen, were enriched for inflammatory and actin remodeling pathways, respectively. Single-cell RNA-sequencing confirmed sex-specific network activity in plaque vascular smooth muscle cells. Subcellular phenotyping identified a sex-specific gene expression program within GRNyellowgreen enriched for contractile and vascular development pathways. Bayesian network modeling identified MYH9 (myosin heavy chain 9) as a key driver gene. Elevated MYH9 abundance was associated with increased smooth muscle cell content and reduced lipid content in female carotid plaques compared with males, consistent with fibrous plaque features. Proteomic analyses confirmed MYH9 upregulation in female fibrous plaques and association with stable plaque characteristics.CONCLUSIONSThese findings identify MYH9 as a regulator of female-biased fibrous plaque biology and highlight the importance of sex-specific network regulation in atherosclerosis.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"56 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deletion of PKM2 in Macrophages Promotes Stabilization but Not Regression of Atherosclerotic Plaques.","authors":"Flávio Dionísio,Yeqian Zhu,Filip Prica,Linda Andersson,Xiaoxin Li,Sara Bagur Cardona,Elisabeth Raatz,Dilraj Kaur,Martin E Kirmaier,Anna Gisslinger,Irena Ljungcrantz,Lena Sundius,Tobias Weinberger,Jan Nilsson,Sebastian Theurich,Isabel Gonçalves,Eva Bengtsson,Steffen Massberg,Harry Björkbacka,Christian Schulz,Lukas Tomas","doi":"10.1161/circresaha.125.327091","DOIUrl":"https://doi.org/10.1161/circresaha.125.327091","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"111 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolomics of Right Ventricular Function in Pulmonary Hypertension.","authors":"Jonathan Chacon-Barahona,Samuel J Chung,Jonah D Garry,Robert Frantz,Franz Rischard,Paul M Hassoun,Stephen C Mathai,Catherine E Simpson,Gerald Beck,Nicholas S Hill,Jane A Leopold,Aaron B Waxman,Erika B Rosenzweig,Barry A Borlaug,Monica Mukherjee,Rebecca Vanderpool,Miriam Jacob,Reena Mehra,Margaret M Park,J Emanuel Finet,Samar Farha,Gabriele Grunig,Deborah Kwon,Suzy Comhair,Serpil Erzurum,John Barnard,Bo Hu,Christine L Jellis,Alexandra Christin Racanelli,Jan Krumsiek,Evan L Brittain,Anna Hemnes,Evelyn Horn, ","doi":"10.1161/circresaha.125.327342","DOIUrl":"https://doi.org/10.1161/circresaha.125.327342","url":null,"abstract":"BACKGROUNDThe metabolic mechanisms underlying right ventricular (RV) dysfunction are poorly understood, particularly outside of group 1 pulmonary hypertension (PH). We aimed to identify metabolites and pathways associated with RV systolic function and explored whether associations differed by pulmonary vascular resistance, PH group 1 status, and sex.METHODSWe analyzed data from the multicenter PVDOMICS (Pulmonary Vascular Disease Phenomics) cohort. RV systolic function metrics included fractional area change (echo), global longitudinal strain (echo), and ejection fraction (cardiac magnetic resonance). We used linear regression adjusted for age, sex, body mass index, and PH group to assess associations between metabolites and RV function. Pathway enrichment analyses were used to identify pathways significantly associated with RV function. Interaction terms were assessed to determine whether metabolite associations were modified by pulmonary vascular resistance, group 1 PH status, or sex. Least absolute shrinkage and selection operator regression was used to develop metabolite-based scores for RV function, and prognostic performance was assessed.RESULTSThere were 979 participants with plasma metabolomics and RV function data. Linear regression identified 170 metabolites that were significantly associated with all 3 RV metrics. Androgenic steroid, gamma-glutamyl amino acid, polyamine, vitamin A, fatty acid, and sterol pathways are most strongly associated with RV systolic function. Two metabolites interacted with group 1 PH status, and 6 interacted with pulmonary vascular resistance. Four androgenic steroids are associated more strongly with RV systolic function in females compared with males. Metabolite-based scores were prognostically equivalent to RV systolic function metrics and less accurate than REVEAL Lite 2 scores.CONCLUSIONSWe provide a blueprint of metabolites and metabolic pathways associated with RV systolic function across the spectrum of PH. Novel links to vitamin A and glutathione metabolites were observed. We detected few metabolites that associated with RV systolic function differentially by group 1 PH status or degree of pulmonary vascular resistance elevation. Androgenic steroids may associate more strongly with RV systolic function in females compared with males.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"128 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversible Fibroblast Trajectories Regulated by MR Underlie Diastolic Dysfunction.","authors":"David Meral,Argen Mamazhakypov,Duygu Koca,Debanjan Mukherjee,Christos Kamaras,Ramona Emig,Rémi Peyronnet,Sebastian Preißl,Achim Lother","doi":"10.1161/circresaha.125.327301","DOIUrl":"https://doi.org/10.1161/circresaha.125.327301","url":null,"abstract":"BACKGROUNDHeart failure with preserved ejection fraction (HFpEF) is a major health issue of our time. The pathophysiology of HFpEF is diverse, linked to comorbidities, such as kidney disease or obesity, and different from heart failure with reduced ejection fraction. As a consequence, treatment options are still limited. Recent clinical trials indicate beneficial effects of MR (mineralocorticoid receptor) antagonists in HFpEF, but the underlying mechanisms are incompletely understood.METHODS AND RESULTSWe treated male and female mice with aldosterone and a high salt-diet to induce a preclinical cardiorenal HFpEF-like phenotype. Diastolic dysfunction and structural remodeling were comparable in both sexes and, of note, largely reversible after aldosterone withdrawal. Single-nucleus RNA sequencing of left ventricles indicated the greatest change in gene expression after aldosterone treatment in cardiomyocytes, endothelial cells, and fibroblasts. In response to aldosterone, we observed a shift towards a fibroblast subpopulation that is distinct from the canonical myofibroblast population typically seen in heart failure with reduced ejection fraction. Comparison with high-fat diet-induced HFpEF showed an overlapping upregulation of typical MR target genes in both models. To validate the functional consequence of this finding, we treated mice with fibroblast-specific MR deletion (MRTCF21Cre). In contrast to a previous study in heart failure with reduced ejection fraction, MR deletion prevented the onset of diastolic dysfunction, suggesting different roles for fibroblast MR in heart failure subtypes.CONCLUSIONSDiastolic dysfunction is associated with a fibroblast subtype that is different from the myofibroblasts observed in heart failure with reduced ejection fraction. MR activation is an overlapping feature of cardiorenal and cardiometabolic disease models. Further, MR deletion from fibroblasts prevents disease progression, suggesting that the beneficial effects of MR antagonists in HFpEF are related to inhibition of fibroblast MR.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"128 1","pages":""},"PeriodicalIF":20.1,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147680662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking Mitochondria: The Extracellular Dimension.","authors":"Laura Pena-Couso, Magdalena Makuch, Jose Angel Nicolas-Avila","doi":"10.1161/CIRCRESAHA.125.326988","DOIUrl":"10.1161/CIRCRESAHA.125.326988","url":null,"abstract":"<p><p>Mitochondria are essential organelles that transform the energy contained in metabolic substrates into ATP while supporting numerous cellular processes. Traditionally regarded as strictly intracellular, growing evidence now demonstrates that mitochondria and mitochondria-derived components can also be released into the extracellular space, giving rise to extracellular mitochondria. extracellular mitochondria display remarkable heterogeneity, ranging from intact organelles to individual molecular components, free to vesicle-encapsulated structures, and with functional states spanning from severely damaged to metabolically active. Their release is mediated by tightly regulated mechanisms in both living and dying cells, and is influenced by cellular stress, activation state, and pathways that control mitochondrial selection, compartmentalization, trafficking, and extrusion. Extracellular release fulfills multiple functions across the organism, including quality control, modulation of cellular identity, inflammatory signaling, and functional support of recipient cells. In the cardiovascular system, extracellular mitochondria contribute to both homeostasis and disease progression. This review summarizes current knowledge of extracellular mitochondria forms, mechanisms of release, and pathophysiological relevance, and highlights their emerging potential as therapeutic targets in cardiovascular pathophysiology and beyond.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"138 8","pages":"e326988"},"PeriodicalIF":16.2,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Transfer to Endothelial Cells: Mechanisms, Evidence, and Therapeutic Potential.","authors":"Gwang-Bum Im,Juan M Melero-Martin","doi":"10.1161/circresaha.125.326982","DOIUrl":"https://doi.org/10.1161/circresaha.125.326982","url":null,"abstract":"Mitochondria are increasingly recognized as central regulators of vascular health, shaping endothelial cell function through roles that extend far beyond energy production. In addition to coordinating redox balance, calcium dynamics, and biosynthetic support, recent studies have revealed that mitochondria participate in intercellular communication, with evidence of transfer events emerging in vascular contexts. Parallel efforts have advanced the deliberate delivery of exogenous mitochondria from preclinical proof-of-principle studies to first-in-human trials, demonstrating that freshly isolated organelles can be harvested and administered in real-time to critically ill patients with favorable early outcomes. The mechanisms underlying these benefits remain incompletely defined, and strategies for efficient and scalable delivery are still emerging. In this review, we prioritize recent evidence linking mitochondrial function to endothelial cell physiology, highlight the nascent but growing field of mitochondrial transfer in the vasculature, and examine how mitochondrial transplantation is evolving from experimental concept to clinical translation. Together, these advances point to new therapeutic avenues for preserving vascular integrity and treating disease.","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"20 1","pages":"e326982"},"PeriodicalIF":20.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}