Evidence map›Paper›PMID 39656872›Full record

ArticleFunction (Oxford, England)2025

Increased Anion Exchanger-1 (Band 3) on the Red Blood Cell Membrane Accelerates Scavenging of Nitric Oxide Metabolites and Predisposes Hypertension Risks.

Li-Yang Chen, Pin-Lung Chen, Si-Tse Jiang, Hui-Lin Lee, Yen-Yu Liu, Alysa Chueh, Jing-Heng Lin, Caleb G Chen, Chung-Lieh Hung, Kate Hsu

Abstract read
In one paragraph

Article in Function (Oxford, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Li-Yang ChenThe Laboratory of Immunogenetics, Department of Medical Research, MacKay Memorial Hospital, Tamsui, New Taipei City 251020, Taiwan.
Pin-Lung ChenThe Laboratory of Immunogenetics, Department of Medical Research, MacKay Memorial Hospital, Tamsui, New Taipei City 251020, Taiwan.ORCID 0000-0001-6364-1831
Si-Tse JiangNational Laboratory Animal Center, National Applied Research Laboratories, Taipei 106214, Taiwan.
Hui-Lin LeeThe Laboratory of Immunogenetics, Department of Medical Research, MacKay Memorial Hospital, Tamsui, New Taipei City 251020, Taiwan.
Yen-Yu LiuDepartment of Critical Care Medicine, MacKay Memorial Hospital, Tamsui, New Taipei City 251020, Taiwan.
Alysa ChuehThe Laboratory of Immunogenetics, Department of Medical Research, MacKay Memorial Hospital, Tamsui, New Taipei City 251020, Taiwan.
Jing-Heng LinThe Laboratory of Immunogenetics, Department of Medical Research, MacKay Memorial Hospital, Tamsui, New Taipei City 251020, Taiwan.
Caleb G ChenDepartment of Hematology, MacKay Memorial Hospital, Taipei 104217, Taiwan.
Chung-Lieh HungInstitute of Biomedical Sciences, MacKay Medical College, New Taipei City 252005, Taiwan.
Kate HsuThe Laboratory of Immunogenetics, Department of Medical Research, MacKay Memorial Hospital, Tamsui, New Taipei City 251020, Taiwan.ORCID 0000-0003-1009-0997

Funding

Mackay Memorial Hospital MMH 111-26Taiwan National Science and Technology Council
6 · The paper itself

Abstract

The erythrocyte membrane is highly specialized with ∼1 million anion exchanger-1 (AE1) per cell for rapid membrane permeation of HCO3-(aq), as most blood CO2(g) is carried in this hydrated anionic form. People with the GP.Mur blood type have more AE1 on their erythrocyte membrane, and they excrete CO2(g) more efficiently. Unexpectedly, GP.Mur/increased AE1 is also associated with higher blood pressure (BP). To solve this, we knocked the human GYP.Mur gene into C57BL/6J mice at 3'-UTR of GYPA to generate GPMur knock-in (KI) mice. KI of human GYP.Mur increased murine AE1 expression on the red blood cells (RBC). GPMur KI mice were naturally hypertensive, with normal kidney functions and lipid profiles. Blood NO3- [the stable nitric oxide (NO) reservoir] was significantly lower in the GPMur mice. GPMur KI also accelerated AE1-mediated NO2- influx into the RBCs and intraerythrocytic NO2-/NO processing. From tests with different categories of antihypertensives, hypertension in GPMur mice responded best to direct arterial vasodilator hydralazine, suggesting that vasodilator deficiency is the leading cause of "GPMur/AE1-triggered hypertension." In conclusion, we showed that GPMur/increased AE1 predisposed hypertension risks. Mechanistically, higher AE1 expression increased RBC membrane permeability for NO2- and consequently accelerated erythroid NO2-/NO metabolism; this is associated with lower NO bioavailability and higher BP. As hypertension affects a quarter of the world population and GP.Mur is a common Southeast Asian (SEA) blood type, this work may serve as a primer for "GPMur (biomarker)-based" therapeutic development for hypertension.

Indexed as

Anion Exchange Protein 1, ErythrocyteErythrocyte MembraneHypertensionNitric OxideAnimalsBlood PressureHumansMaleMiceMice, Inbred C57BLAnion Exchange Protein 1, ErythrocyteNitric Oxideanion exchanger-1 (AE1anion transportband 3)blood pressureglycophorinGP.Mur (Mi.III)hypertensionMiltenberger blood typenitric oxidenitritered blood cell

Identifiers

PMID39656872
PMCPMC11815584

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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.