Circulation research最新文献

{"title":"TFEB Antagonizes Cardiac Hypertrophy and Failure by Enhancing Lysosomal Capacity and Mitochondrial Function.","authors":"Daniel Daou, Subhajit Das Gupta, Anip Anand, Herman I May, Nan Jiang, Sebastián Urquiza-Zurich, Camila I Irion, Anwarul Ferdous, Valeria Garrido-Moreno, Mayarling F Troncoso, Nicholas Nguyen, Lisandro Maya-Ramos, Diana Dad Zada, Francisco Olivares-Silva, Guo Chen, Feng Wu, Abhinav Diwan, Michael Kinter, Vinicius Maracaja-Coutinho, Beverly A Rothermel, Luke I Szweda, Sergio Lavandero, Thomas G Gillette, Joseph A Hill","doi":"10.1161/CIRCRESAHA.125.328083","DOIUrl":"10.1161/CIRCRESAHA.125.328083","url":null,"abstract":"<p><strong>Background: </strong>Pathological cardiac remodeling and afterload-induced increases in energy demand contribute to heart failure (HF). Lysosome-assisted processes, such as autophagy, coupled with alterations in mitochondrial oxidative capacity, are critical regulators of this response. Furthermore, the lysosome is a hub for multiple signaling pathways governing hypertrophic growth. TFEB (transcription factor EB) has emerged as a key regulator of lysosomal genes and mitochondrial function in multiple tissues, especially in response to external stress.</p><p><strong>Methods: </strong>Leveraging a cardiomyocyte-specific TFEB knockout mouse (CTKO), pressure overload was induced by transverse aortic constriction (TAC) to elucidate the role of TFEB under hypertrophic stress conditions. Echocardiography was employed to assess cardiac function, and hearts were subsequently harvested for transcriptomic, proteomic, and metabolomic analyses. To glean further insight into the molecular mechanisms involved, we studied neonatal rat ventricular myocytes exposed to phenylephrine, an in vitro model of cardiomyocyte hypertrophy.</p><p><strong>Results: </strong>We report that TFEB is rapidly activated and translocates to the nucleus in cardiomyocytes exposed to hypertrophic stress conditions, triggering a lysosomal gene program independent of autophagy gene changes. At baseline, contractile function measured by echocardiography appeared normal in these mice compared with their Cre-negative littermates. However, in pressure-overload stress induced by TAC, CTKO mice manifested an amplified hypertrophic response, leading rapidly to HF. Unlike WT hearts, CTKO hearts failed to increase lysosomal capacity after TAC. They manifested an increase in the steady-state levels of autophagosome-associated proteins, such as LC3II and p62, as well as accumulation of ubiquitinated proteins, suggesting a defect in protein turnover. Interestingly, CTKO mice harbored altered mitochondrial structure, reduced oxidative capacity, and reduced abundance of peroxisome PGC-1α-b (proliferator-activated receptor-1 alpha-b). Furthermore, CTKO hearts manifested reduced expression of key enzymes within metabolic pathways essential for normal myocardial metabolism, including fatty acid metabolism, carbon metabolism, and branched-chain amino acid metabolism. Surprisingly, AMPK (AMP-activated protein kinase) signaling, while normal at baseline, was significantly decreased in CTKO hearts after TAC. This reliance on TFEB for growth trigger-induced AMPK signaling was also observed in vitro in cells exposed to phenylephrine, as were the antihypertrophic effects of TFEB activation, supporting a direct role of TFEB in this process. Finally, we report that exogenous activation of AMPK in the absence of TFEB can completely rescue the exacerbated hypertrophic response both in vitro and in vivo, independent of lysosomal function. Notably, blunting of the hypertrophic response did not impact the de","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"e328083"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13331260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257507","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":"Protective B Cell? B1a-Derived Natural IgM in the Immunology of Hypertension.","authors":"Ashley L Mutchler","doi":"10.1161/CIRCRESAHA.126.329229","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.126.329229","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 4","pages":"e329229"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629616","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":"Single Cell Proteomics to Spatial Multiomics in Cardiovascular Disease: Foundations, Technologies, and Biological Insights.","authors":"Aleksandra Binek, Peggi M Angel","doi":"10.1161/CIRCRESAHA.126.327684","DOIUrl":"10.1161/CIRCRESAHA.126.327684","url":null,"abstract":"<p><p>It is now apparent that cardiac form and function are governed at a system level by an integrated collective of heterogeneous single-cell programs that together regulate tissue homeostasis, drive disease emergence, and shape individualized responses to therapy. Current advances in single-cell proteomics and spatial multiomics by mass spectrometry imaging allow systematic dissection of clinically defined cardiovascular tissues with an unprecedented molecular resolving power, yet remain relatively underutilized in cardiovascular research. This compendium review works to stimulate new research into spatial regulation of the heart, emphasizing integration of single-cell proteomic regulation with comprehensive multiomic mass spectrometry imaging studies. In this context, we outline conceptual foundations, technological innovations, and biological insights that have resulted in the current success of single-cell proteomic and spatial multiomic analyses in cardiovascular disease. We provide an experimental design knowledge base of critical components in single-cell proteomics and spatial workflows by mass spectrometry imaging, essential for generating robust and reproducible data sets that are interpretable by advanced computational methods. Key cardiovascular discoveries by single-cell proteomics and multiomic mass spectrometry imaging are reviewed, highlighting how these approaches have provided new molecular insights into cardiac cell programming.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 4","pages":"e327684"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629667","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":"Decoding Cardiovascular Disease Through Spatial Proteomics.","authors":"Min Ma, Yingyi Lian, Erfei Shang, Chao Xue, Maosheng Wei, Ming Zhang, Niveda Sundararaman, Sarah J Parker, Jennifer E Van Eyk, Jun Qu","doi":"10.1161/CIRCRESAHA.126.327475","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.126.327475","url":null,"abstract":"<p><p>Cardiovascular function is tightly linked to tissue architectures, where the spatial organization of cells, extracellular matrix (ECM), vascular networks, and remodeling processes governs physiological performance and disease progression. Spatial proteomics has, therefore, emerged as a powerful framework for understanding cardiovascular biology and cardiovascular disease mechanisms by revealing spatially organized protein regulation across various physiological and pathological states. In this review, we focus on spatial proteomics strategies most relevant to cardiovascular research and discuss their applications through representative examples. These approaches can be broadly categorized into region-of-interest-based methods, which enable precise characterization of localized cellular heterogeneity, and tissue mapping strategies, which capture spatial organization and biologically relevant region-to-region variability across larger tissue domains. In addition, spatial proteomics platforms differ in their capacity for targeted or untargeted protein analysis, influencing both proteome coverage and their suitability for hypothesis-driven versus discovery-based studies. We evaluate the strengths and limitations of state-of-the-art technologies across 3 key parameters, molecular depth, spatial coverage, and spatial resolution, and discuss how these parameters shape study design and biological understanding. Building on these considerations, we argue that a comprehensive understanding of cardiovascular tissue biology requires spatial proteomics strategies that capture both localized molecular details and spatial organization across large tissue areas, as neither alone is sufficient to explain complex tissue behavior. We propose an integrated workflow in which untargeted, whole-tissue mapping of thousands of proteins is first used to unbiasedly discover spatial patterns and generate hypotheses by identifying candidate regions and proteins of interest, followed by hypothesis testing and validation using high-precision region-of-interest-based proteomics and targeted protein imaging. This sequential framework leverages the complementary strengths of tissue-wide mapping and region-of-interest-based approaches to provide multiscale, mechanistic insights into spatially organized disease processes. Finally, we discuss emerging directions that are poised to expand the scope of spatial proteomics in cardiovascular research.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 4","pages":"e327475"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629597","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":"Meet the First Authors.","authors":"","doi":"10.1161/RES.0000000000000764","DOIUrl":"https://doi.org/10.1161/RES.0000000000000764","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 4","pages":"e000764"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629607","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":"STING Goes Mitochondrial: A Metabolic Regulator in Diabetic Cardiomyopathy.","authors":"Giulia Guerra, Alessandra Ghigo","doi":"10.1161/CIRCRESAHA.126.329116","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.126.329116","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 4","pages":"e329116"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629613","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":"Correction to: Dectin-2 Deficiency Modulates Th1 Differentiation and Improves Wound Healing After Myocardial Infarction.","authors":"Xiaoxiang Yan, Hang Zhang, Qin Fan, Jian Hu, Rong Tao, Qiujing Chen, Yoichiro Iwakura, Weifeng Shen, Lin Lu, Qi Zhang, Ruiyan Zhang","doi":"10.1161/RES.0000000000000763","DOIUrl":"https://doi.org/10.1161/RES.0000000000000763","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 4","pages":"e000763"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629641","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":"Defining Actionable Cell States in Cardiovascular Disease Through Single-Cell and Spatial Technologies.","authors":"Sarah J Parker, Jennifer E Van Eyk","doi":"10.1161/CIRCRESAHA.126.329382","DOIUrl":"10.1161/CIRCRESAHA.126.329382","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 4","pages":"e329382"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629619","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":"Decoding Cardiac Development and Maturation at Single-Cell and Spatial Transcriptomic Resolution.","authors":"Biyi Li, Xihe Liu, Sean Murphy, Emmanouil Tampakakis, Chulan Kwon","doi":"10.1161/CIRCRESAHA.125.327473","DOIUrl":"10.1161/CIRCRESAHA.125.327473","url":null,"abstract":"<p><p>Recent advances in single-cell transcriptomics have revolutionized our understanding of cardiac development and maturation by resolving cellular heterogeneity, delineating lineage trajectories, and uncovering gene regulatory networks and intercellular signaling at unprecedented resolution. The heart develops through a tightly coordinated spatiotemporal process that extends from early organogenesis through postnatal maturation. Despite major progress, key questions remain unresolved, including the localization and function of rare progenitor populations and the mechanisms that guide cardiomyocyte maturation and loss of regenerative capacity. Spatial transcriptomics has emerged as a powerful complement to single-cell profiling because it preserves the native tissue architecture and reveals how gene expression is organized within anatomic context. Although many spatial studies to date have focused on cardiac disease and injury, emerging developmental data sets spanning embryonic to postnatal stages now enable reconstruction of spatially resolved trajectories of heart formation. Here, we review key findings and limitations from recent single-cell and spatial transcriptomic studies of heart development and maturation and discuss how integrative approaches and advanced computational tools are redefining the molecular and spatial logic of cardiogenesis. These insights are expected to greatly accelerate future regenerative and translational research.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 4","pages":"e327473"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13425939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629604","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":"TFEB at the Crossroads: From Cellular Mechanism to Precision Care.","authors":"Ivor J Benjamin, Jacek Zielonka","doi":"10.1161/CIRCRESAHA.126.329311","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.126.329311","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 4","pages":"e329311"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629638","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}