ArticleCirculation2013
Long-term heart transplant survival by targeting the ionotropic purinergic receptor P2X7.
Article in Circulation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 108 citations in OpenAlex.
- Brain Death-Induced Systolic Ventricular Dysfunction and Its Association With NLRP3-Related Inflammatory Signaling in a Murine Model.Annals of transplantation · 2026Article
- Host-directed therapeutic strategies against apicomplexan parasites: targeting purinergic P2 receptors.Purinergic signalling · 2026Review
- Purinoreceptor P2X7 in Extracellular ATP-Mediated Inflammation through the Spectrum of Kidney Diseases and Kidney Transplantation.Journal of the American Society of Nephrology : JASN · 2025Review
- ATP/P2X7 receptor signal aggravates ischemic stroke injury by activating Th17 cells via STAT3/IL-21 pathway.Frontiers in immunology · 2025Article
- Article
- Expression in skin biopsies supports genetic evidence linking CAMKK2, P2X7R and P2X4R with HIV-associated sensory neuropathy.Journal of neurovirology · 2023Article
- The Role of P2X7 Purinoceptors in the Pathogenesis and Treatment of Muscular Dystrophies.International journal of molecular sciences · 2023Review
- An agent-based model of cardiac allograft vasculopathy: toward a better understanding of chronic rejection dynamics.Frontiers in bioengineering and biotechnology · 2023Article
- Toll-like receptors and damage-associated molecular patterns in the pathogenesis of heart transplant rejection.Molecular and cellular biochemistry · 2022Review
- Review
- The Role of Purinergic Signaling in Heart Transplantation.Frontiers in immunology · 2022Review
- miR-21 antagonism reprograms macrophage metabolism and abrogates chronic allograft vasculopathy.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- From purines to purinergic signalling: molecular functions and human diseases.Signal transduction and targeted therapy · 2021Review
- Article
- P2X7 Receptor-Mediated Inflammation in Cardiovascular Disease.Frontiers in pharmacology · 2021Review
- Untangling Local Pro-Inflammatory, Reparative, and Regulatory Damage-Associated Molecular-Patterns (DAMPs) Pathways to Improve Transplant Outcomes.Frontiers in immunology · 2021Review
- P2X7 Receptor at the Crossroads of T Cell Fate.International journal of molecular sciences · 2020Review
- Extracellular nucleotide signaling in solid organ transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2020Review
- DAMP-sensing receptors in sterile inflammation and inflammatory diseases.Nature reviews. Immunology · 2020Review
- Extracellular Nucleotides and P2 Receptors in Renal Function.Physiological reviews · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundHeart transplantation is a lifesaving procedure for patients with end-stage heart failure. Despite much effort and advances in the field, current immunosuppressive regimens are still associated with poor long-term cardiac allograft outcomes, and with the development of complications, including infections and malignancies, as well. The development of a novel, short-term, and effective immunomodulatory protocol will thus be an important achievement. The purine ATP, released during cell damage/activation, is sensed by the ionotropic purinergic receptor P2X7 (P2X7R) on lymphocytes and regulates T-cell activation. Novel clinical-grade P2X7R inhibitors are available, rendering the targeting of P2X7R a potential therapy in cardiac transplantation. METHODS AND
resultsWe analyzed P2X7R expression in patients and mice and P2X7R targeting in murine recipients in the context of cardiac transplantation. Our data demonstrate that P2X7R is specifically upregulated in graft-infiltrating lymphocytes in cardiac-transplanted humans and mice. Short-term P2X7R targeting with periodate-oxidized ATP promotes long-term cardiac transplant survival in 80% of murine recipients of a fully mismatched allograft. Long-term survival of cardiac transplants was associated with reduced T-cell activation, T-helper cell 1/T-helper cell 17 differentiation, and inhibition of STAT3 phosphorylation in T cells, thus leading to a reduced transplant infiltrate and coronaropathy. In vitro genetic upregulation of the P2X7R pathway was also shown to stimulate T-helper cell 1/T-helper cell 17 cell generation. Finally, P2X7R targeting halted the progression of coronaropathy in a murine model of chronic rejection as well.
conclusionsP2X7R targeting is a novel clinically relevant strategy to prolong cardiac transplant survival.
Indexed as
Identifiers
What OpenQuestion holds
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.