Circulation research最新文献

{"title":"Meet the First Authors.","authors":"","doi":"10.1161/RES.0000000000000766","DOIUrl":"https://doi.org/10.1161/RES.0000000000000766","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 5","pages":"e000766"},"PeriodicalIF":18.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758982","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":"Cannabis Is Not Vascularly Inert: Proatherogenic Inflammation in Youth.","authors":"Caitlin Giannis, Mark Chandy, Leila Mohammadi, Naomi M Hamburg","doi":"10.1161/CIRCRESAHA.126.329347","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.126.329347","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 5","pages":"e329347"},"PeriodicalIF":18.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757522","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":"Shifting the Balance: Mitochondrial Heteroplasmy as a Driver of Cardiac Disease.","authors":"Andriana Papadaki, Itamar Braga Dias, Christoph Maack, Peter van der Meer, Nils Bomer","doi":"10.1161/CIRCRESAHA.126.328769","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.126.328769","url":null,"abstract":"<p><p>Mitochondrial heteroplasmy represents a fundamental determinant of mitochondrial function and disease, yet its consequences vary across different tissues. Although mitotic tissues possess mechanisms, such as cell division and mitochondrial turnover, to dilute or remove deleterious variants, postmitotic tissues lack this renewal capacity and are disproportionately vulnerable. Neuromuscular and neurodegenerative disorders have illustrated the impact of heteroplasmic mutations, but the (postmitotic) heart remains underexplored. Current reliance on blood-derived samples provides only an indirect view of cardiac heteroplasmy, highlighting the need for alternative approaches, such as endomyocardial biopsies and human induced pluripotent stem cell-derived cardiomyocytes. Expanding cardiac-focused research is essential for identification, clarifying pathogenesis, improving risk stratification, and guiding patient monitoring. Emerging therapies, including mitochondrial transplantation and mitochondrial-targeted DNA editing, demonstrate potential to modulate heteroplasmy and restore equilibrium. Integrating these strategies with precision medicine will be vital for addressing tissue-specific vulnerabilities. Ultimately, bridging the gap in cardiac heteroplasmy research will be critical for translating basic mitochondrial biology into meaningful clinical advances.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 5","pages":"e328769"},"PeriodicalIF":18.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763918","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":"Adipose-Myocardial Border in Atrial Fibrillation.","authors":"Timothy Fitzgibbons, Khanh-Van Tran","doi":"10.1161/CIRCRESAHA.126.329119","DOIUrl":"https://doi.org/10.1161/CIRCRESAHA.126.329119","url":null,"abstract":"","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":"139 5","pages":"e329119"},"PeriodicalIF":18.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13474729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148757729","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":"Aging Disrupts L-type Ca²⁺ Channel Organization and Function in Pacemaker Cells.","authors":"Oscar Vivas, Matthias Baudot, Roxanne Madden, Wendy L Piñon-Teal, Martina S Hunt, Sabrina Choi, Roya Pournejati, Victor A Flores-Tamez, L Fernando Santana, Claudia M Moreno","doi":"10.1161/CIRCRESAHA.125.327894","DOIUrl":"10.1161/CIRCRESAHA.125.327894","url":null,"abstract":"<p><strong>Background: </strong>Every heartbeat is initiated by a spontaneous electrical signal generated inside the cardiac pacemaker. This signal depends on the coordinated activity of ion channels, where voltage-gated L-type calcium channels play a central role. All mammals experience a progressive decline in pacemaker rate with age, which in humans can become pathological and drive the need for artificial pacemaker implantation. Yet the mechanisms underlying this age-associated slowdown remain incompletely understood.</p><p><strong>Methods: </strong>We combined patch-clamp electrophysiology, single-channel recording, calcium imaging, immunocytochemistry, and super-resolution microscopy to investigate L-type calcium channel density, organization, and function in sinoatrial node pacemaker cells from young and old mice.</p><p><strong>Results: </strong>Aging reduced L-type calcium channel density at the plasma membrane, disrupted channel clustering, and decreased open probability, collectively diminishing calcium current density by 50%. Pharmacological enhancement of channel open probability with Bay K 8644 was sufficient to accelerate diastolic depolarization and restore pacemaker rate in old cells to young levels. These channel alterations were paralleled by a decline in caveolin-3 expression. Disrupting caveolae in young cells recapitulated the loss of channel clustering, pointing to caveolae as a structural basis for the age-associated channel alterations.</p><p><strong>Conclusions: </strong>Aging impairs L-type calcium channel organization and function in cardiac pacemaker cells. This impairment is mediated by an age-associated reduction of caveolae, key membrane microdomains for channel organization. The resulting decline in L-type calcium channel density and activity is an important driver of the age-associated slowdown of the cardiac pacemaker.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"e327894"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13418876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276310","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":"Single-Cell Studies Advance Understanding of the Genetic and Molecular Basis of Atherosclerosis.","authors":"Daniel Y Li, João P Monteiro, Quanyi Zhao, Nathan O Stitziel, Thomas Quertermous","doi":"10.1161/CIRCRESAHA.125.327472","DOIUrl":"10.1161/CIRCRESAHA.125.327472","url":null,"abstract":"<p><p>Atherosclerosis is a chronic disease of the arterial wall driven by complex interactions between vascular, immune, and stromal cells. For decades, our understanding of plaque biology relied on bulk assays that masked the underlying cellular heterogeneity. The development of single-cell and spatial genomics now enables the dissection of these multicellular systems with unprecedented granularity. These technologies have revealed the dynamic nature of vascular smooth muscle and endothelial cells, providing a framework to link genetic risk to specific transcriptional programs and cellular phenotypes. Single-cell RNA sequencing and single-cell epigenome sequencing (single-cell assay for transposase-accessible chromatin with sequencing) have redefined vascular cell biology, revealing intermediate phenotypic states and transcriptional regulators of disease progression. Recent advances in spatially resolved transcriptomics have begun to link these molecular profiles to their anatomic context within the plaque microenvironment, informing on cell-cell signaling pathways. Integrating genetic risk with single-cell data is illuminating how noncoding variants converge on specific vascular cell types and gene-regulatory networks. In this review, we summarize key technological advances in single-cell RNA sequencing, single-cell assay for transposase-accessible chromatin with sequencing, and spatial transcriptomics. Furthermore, we highlight recent biological discoveries and discuss emerging approaches, particularly clustered regularly interspaced short palindromic repeats perturbation-based single-cell methods, which are poised to bridge causal genetics and functional vascular biology in atherosclerosis.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"e327472"},"PeriodicalIF":18.0,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148223758","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":"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":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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":"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":"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":"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}