ArticleThe Journal of clinical investigation2023
Impaired T cell IRE1α/XBP1 signaling directs inflammation in experimental heart failure with preserved ejection fraction.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 39 citations in OpenAlex.
- Heart-specific T cell responses: from antigens to disease mechanisms.Nature reviews. Cardiology · 2026Review
- Metformin alleviates aging-associated periodontitis via NRF2-mediated restoration of the IRE1α dependent unfolded protein response.Bioactive materials · 2026Article
- Cardiac fibroblast diversity in HFpEF: states, niches, interorgan drivers and targets.Nature reviews. Cardiology · 2026Review
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
- Inflammation, metabolism, and aging in heart failure with preserved ejection fraction: Mechanisms and treatment perspectives.Journal of translational internal medicine · 2026Article
- T Cell Receptor Repertoires Across the Continuum of Vascular, Myocardial, and Age-Related Diseases.Immunological reviews · 2026Review
- Microvascular endothelial scavenger receptor class B type I protects against heart failure with preserved ejection fraction by inhibiting T-cell cardiotropism.EMBO molecular medicine · 2026Article
- Inflammatory-lipid residual risk phenotypes delineate the HFpEF probability spectrum independent of cardiometabolic mediation.BMC cardiovascular disorders · 2026Article
- Review
- International Utah cardiac recovery symposium (U-CARS) 2025:translational and basic science proceedings.Heart failure reviews · 2026Review
- Organelle regulation of SUMOylation: regulatory mechanisms and therapeutic application.Journal of advanced research · 2026Review
- T cell-derived IFNγ instructs ECM crosslinking by cardiac fibroblasts through LOXL3 in experimental cardiometabolic HFpEF.bioRxiv : the preprint server for biology · 2026Article
- Cellular Interactions and Immunometabolic Mechanisms in Heart Failure With Preserved Ejection Fraction: From Molecular Mechanisms to Clinical Evidence.Circulation. Heart failure · 2026Review
- Lymphocyte-To-Monocyte Ratio is Partially Mediated in Age-Related Cardiovascular Mortality in HFpEF: Immunosenescence, Inflamm-Aging, and Longevity.Reviews in cardiovascular medicine · 2026Article
- Impaired antigen clearance of macrophages associates with heart failure and non-obstructive azoospermia: insights from transcriptomics, in silico knockout, andFrontiers in immunology · 2026Article
- Combined metabolic stress and nitric oxide synthase inhibition induces tissue-specific remodeling across cardiovascular and hematopoietic compartments during obesity.Frontiers in cardiovascular medicine · 2026Article
- Association between systemic immune-inflammation index(SII) and all-cause and cardiovascular mortality in heart failure patients: a single-center retrospective analysis.Frontiers in cardiovascular medicine · 2026Article
- Heart failure with preserved ejection fraction in cancer patients and survivors. A scientific statement of the Heart Failure Association of the ESC and the ESC Council of Cardio-Oncology.European journal of heart failure · 2025Article
- Cardiovascular inflammaging: Mechanisms, consequences, and therapeutic perspectives.Cell reports. Medicine · 2025Review
- Cardiometabolic heart failure with preserved ejection fraction: from molecular signatures to personalized treatment.Cardiovascular diabetology · 2025Review
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Heart failure with preserved ejection fraction (HFpEF) is a widespread syndrome with limited therapeutic options and poorly understood immune pathophysiology. Using a 2-hit preclinical model of cardiometabolic HFpEF that induces obesity and hypertension, we found that cardiac T cell infiltration and lymphoid expansion occurred concomitantly with cardiac pathology and that diastolic dysfunction, cardiomyocyte hypertrophy, and cardiac phospholamban phosphorylation were T cell dependent. Heart-infiltrating T cells were not restricted to cardiac antigens and were uniquely characterized by impaired activation of the inositol-requiring enzyme 1α/X-box-binding protein 1 (IRE1α/XBP1) arm of the unfolded protein response. Notably, selective ablation of XBP1 in T cells enhanced their persistence in the heart and lymphoid organs of mice with preclinical HFpEF. Furthermore, T cell IRE1α/XBP1 activation was restored after withdrawal of the 2 comorbidities inducing HFpEF, resulting in partial improvement of cardiac pathology. Our results demonstrated that diastolic dysfunction and cardiomyocyte hypertrophy in preclinical HFpEF were T cell dependent and that reversible dysregulation of the T cell IRE1α/XBP1 axis was a T cell signature of HFpEF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.