Vikas Kumar
Gautham Yepuri
Gaurav Kumar
Ann Marie Schmidt- 1Diabetes Research Program, Department of Medicine, New York University (NYU) Grossman School of Medicine, New York, NY, United States
- 2Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, United States
Editorial on the Research Topic
Cardiovascular immunometabolism - a complex interplay between the immune system and metabolism in the heart
Heart failure (HF) remains one of the leading causes of morbidity and mortality globally, posing a significant clinical and public health burden (1, 2). While traditionally conceptualized as a condition resulting from hemodynamic and structural dysfunction, HF is now increasingly understood as a complex, multifactorial syndrome (3, 4). It involves intricate interactions among genetic predispositions, environmental exposures, immune dysregulation, chronic inflammation, and metabolic remodeling (5, 6).
This Research Topic centers on immunometabolism, an emerging field that examines how immune responses are shaped by, and in turn shape, cellular metabolic processes. Growing evidence suggests that metabolic dysfunction within immune cells contributes to maladaptive cardiac remodeling and impaired tissue repair (7, 8). Key mechanisms include metabolic reprogramming in innate immune cells, the persistence of trained immunity, and aberrant inflammatory signaling (9). Another major focus is the role of extracellular vesicles (EVs)—membrane-bound particles secreted by virtually all cell types—as mediators of intercellular communication. EVs carry diverse bioactive cargos, including proteins, lipids, metabolites, and non-coding RNAs (e.g., miRNAs, lncRNAs, and circRNAs), and have been implicated in the modulation of immune responses, metabolic signaling, and cardiac remodeling processes in HF (10).
This Research Topic brings together a collection of articles exploring the interplay between immune cells, metabolism, EVs, and non-coding RNAs in the context of HF. These contributions provide valuable insights into the cellular and molecular underpinnings of HF and highlight novel diagnostic and therapeutic avenues.
Key contributions
● Omoto et al. present a comprehensive review of the dual roles of EVs—both protective and pro-inflammatory—during cardiac injury. They explore how EVs modulate immune cell metabolism, particularly in the context of obesity and metabolic syndrome. The authors propose that EV cargo, including endocrine signals, miRNAs, lncRNAs, circRNAs, proteins, and metabolites, can act as upstream regulators of immunometabolic pathways. They also discuss how therapeutic loading of EVs could revolutionize treatment strategies in HF and related metabolic disorders.
● Tu et al. utilized machine learning and bioinformatics to re-analyze multiple microarray datasets, identifying a strong association between cuproptosis-related genes (CRGs) and the pathogenesis of HF. Their multivariable logistic regression models based on CRG expression suggest that cuproptosis modulates both metabolic and immune pathways in HF, offering potential diagnostic biomarkers and therapeutic targets.
● Chen et al. focused on diabetic heart failure, identifying four key CRGs (HSDL2, BCO2, CORIN, and SNORA80E) through bioinformatics analysis of GEO datasets. Among these, LOXL2 was most significantly linked to diabetic HF. The study also constructed an lncRNA–miRNA–mRNA network and predicted MECOM as a key transcription factor driving cuproptosis in cardiomyocytes, advancing our understanding of HF pathogenesis in diabetic patients.
● Huang et al. examined factors contributing to accelerated aging in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). By analyzing clinical data from 216 patients, they developed phenotypic age acceleration (PhenoAgeAccel) metrics and identified several risk factors, including neutrophil count, urea, adenosine deaminase, and TyG index, while cholinesterase was identified as a protective factor. These findings underscore the clinical significance of aging-related biomarkers in T2DM-associated HF.
● Tian et al. investigated the prognostic impact of stress hyperglycemia in critically ill patients with cardiogenic shock using the MIMIC-IV database. Stratifying patients based on stress hyperglycemia ratio (SHR), they found that elevated SHR was associated with longer mechanical ventilation, extended ICU and hospital stays, and increased mortality. Their analysis suggests SHR may serve as a valuable prognostic indicator in this high-risk population.
Collectively, these contributions illuminate the complex interplay between immune responses, metabolic alterations, non-coding RNAs, and extracellular vesicle signaling in the pathophysiology of heart failure. They also underscore the translational potential of targeting these pathways to develop novel diagnostics and therapeutic strategies.
We anticipate that this Research Topic will serve as a comprehensive and insightful resource for researchers investigating the latest advances in immunometabolism and its therapeutic implications in cardiovascular disease.
Author contributions
VK: Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. GY: Formal analysis, Project administration, Writing – review & editing. GK: Project administration, Writing – review & editing. AS: Formal analysis, Investigation, Project administration, Writing – review & editing.
Conflict of interest
The authors declare that there are no commercial or financial relationships that could be construed as a potential conflict of interest in the conduct of this research.
Generative AI statement
The author(s) declare that no Generative AI was used in the creation of this manuscript.
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References
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2. Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol. (2016) 13:368–78. doi: 10.1038/nrcardio.2016.25
3. Sharma K, Kass DA. Heart failure with preserved ejection fraction: mechanisms, clinical features, and therapies. Circ Res. (2014) 115:79–96. doi: 10.1161/CIRCRESAHA.115.302922
4. Kumar V, Santhosh Kumar TR, Kartha CC. Mitochondrial membrane transporters and metabolic switch in heart failure. Heart failure Rev. (2019) 24:255–67. doi: 10.1007/s10741-018-9756-2
5. Ramos-Lopez O, Milagro FI, Riezu-Boj JI, Martinez JA. Epigenetic signatures underlying inflammation: An interplay of nutrition, physical activity, metabolic diseases, and environmental factors for personalized nutrition. Inflammation Res. (2021) 70:29–49. doi: 10.1007/s00011-020-01425-y
6. Kumar V, Bermea KC, Kumar D, Singh A, Verma A, Kaileh M, et al. RelA-mediated signaling connects adaptation to chronic cardiomyocyte stress with myocardial and systemic inflammation in the ADCY8 model of accelerated aging. GeroScience. (2024) 46:4243–62. doi: 10.1007/s11357-024-01121-3
7. Epelman S, Liu PP, Mann DL. Role of innate and adaptive immune mechanisms in cardiac injury and repair. Nat Rev Immunol. (2015) 15:117–29. doi: 10.1038/nri3800
8. Sun L, Yang X, Yuan Z, Wang H. Metabolic reprogramming in immune response and tissue inflammation. Arteriosclerosis thrombosis Vasc Biol. (2020) 40:1990–2001. doi: 10.1161/ATVBAHA.120.314037
9. Ochando J, Mulder WJ, Madsen JC, Netea MG, Duivenvoorden R. Trained immunity—basic concepts and contributions to immunopathology. Nat Rev Nephrol. (2023) 19:23–37. doi: 10.1038/s41581-022-00633-5
Keywords: heart failure, immunometabolism, cuproptosis, extracellular vesicles (EVs), diabetes, and aging
Citation: Kumar V, Yepuri G, Kumar G and Schmidt AM (2025) Editorial: Cardiovascular immunometabolism - a complex interplay between the immune system and metabolism in the heart. Front. Endocrinol. 16:1613774. doi: 10.3389/fendo.2025.1613774
Received: 17 April 2025; Accepted: 18 April 2025;
Published: 30 April 2025.
Edited and Reviewed by:
Gaetano Santulli, Albert Einstein College of Medicine, United StatesCopyright © 2025 Kumar, Yepuri, Kumar and Schmidt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Vikas Kumar, VmlrYXMuS3VtYXJAbnl1bGFuZ29uZS5vcmc=; cGFuY2hhbHZrYXM4OEBnbWFpbC5jb20=