ArticleScience immunology2019
ATP release drives heightened immune responses associated with hypertension.
Article in Science immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- A Paradigm Gap in Host-Pathogen Interaction Studies: Lesson from the COVID-19 Pandemic.Advances in experimental medicine and biology · 2021Pooled it
- High-Dose vs. Standard-Dose Influenza Vaccine in Older Patients With Hypertension: A Post Hoc Analysis of DANFLU-1.Journal of clinical hypertension (Greenwich, Conn.) · 2025Trial
- Neurohumoral Biomarker Profile Associated With Blood Pressure Response After Renal Denervation.Journal of clinical hypertension (Greenwich, Conn.) · 2026Article
- Emerging roles of ferroptosis in modulating the immune landscape of glial tumours.Nature cell biology · 2026Review
- Seasonal PMToxics · 2026Article
- Tubular epithelial cells promote macrophage pyroptosis through PANX1-extracellular ATP-P2X7 signaling in aldosterone-dependent renal injury.Cell death & disease · 2026Article
- Astrocyte-Neuron Crosstalk in Hypertension: Mechanisms and Therapeutic Significance.Reviews in cardiovascular medicine · 2026Review
- Serum amyloid A in HFpEF and cardiometabolic diseases.Basic research in cardiology · 2026Review
- Innate immunity and hypertension: unveiling inflammatory pathways for novel therapies.Frontiers in pharmacology · 2026Review
- A Bibliometric Analysis of P2X7R in Cardiovascular Diseases from 2005 to 2024.Current cardiology reviews · 2026Review
- Interplay Between the Mineralocorticoid System, Inflammation, Hypertension, and Kidney Disease.Kidney360 · 2025Review
- Association between multifactorial control and excess risk of liver diseases in type 2 diabetes: a prospective cohort study.BMJ open diabetes research & care · 2025Article
- Uncovering immune pathways for therapeutic targeting of hypertension.Expert opinion on therapeutic targets · 2025Review
- Cardiovascular-kidney-metabolic syndrome, systemic inflammation, and incident dementia: evidence from 400,740 UK Biobank participants.Diabetology & metabolic syndrome · 2025Article
- 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
- Activation of Adenosine Triphosphate-Gated Purinergic 2 Receptor Channels by Transient Receptor Potential Vanilloid Subtype 4 in Cough Hypersensitivity.Biomolecules · 2025Article
- Article
- ATP/P2X7 receptor/NLRP3 pathway facilitates renal tubular epithelial-myofibroblast transdifferentiation and interstitial fibrosis in rats with unilateral ureteral obstruction.Frontiers in pharmacology · 2025Article
- Calcium ions promote migrasome formation via Synaptotagmin-1.The Journal of cell biology · 2024Article
- Immune mechanisms in the pathophysiology of hypertension.Nature reviews. Nephrology · 2024Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
The cause of most hypertensive disease is unclear, but inflammation appears critical in disease progression. However, how elevated blood pressure initiates inflammation is unknown, as are the effects of high blood pressure on innate and adaptive immune responses. We now report that hypertensive mice have increased T cell responses to antigenic challenge and develop more severe T cell-mediated immunopathology. A root cause for this is hypertension-induced erythrocyte adenosine 5'-triphosphate (ATP) release, leading to an increase in plasma ATP levels, which begins soon after the onset of hypertension and stimulates P2X7 receptors on antigen-presenting cells (APCs), increasing APC expression of CD86. Hydrolyzing ATP or blocking the P2X7 receptor eliminated hypertension-induced T cell hyperactivation. In addition, pharmacologic or genetic blockade of P2X7 receptor activity suppressed the progression of hypertension. Consistent with the results in mice, we also found that untreated human hypertensive patients have significantly elevated plasma ATP levels compared with treated hypertensive patients or normotensive controls. Thus, a hypertension-induced increase in extracellular ATP triggers augmented APC and T cell function and contributes to the immune-mediated pathologic changes associated with hypertensive disease.
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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.