Evidence map›Paper›PMID 37815905›Full record

ArticleAging and disease2024

PNA5, A Novel Mas Receptor Agonist, Improves Neurovascular and Blood-Brain-Barrier Function in a Mouse Model of Vascular Cognitive Impairment and Dementia.

Christina Hoyer-Kimura, Meredith Hay, John P Konhilas, Helena W Morrison, Methawasin Methajit, Joshua Strom, Robin Polt, Victoria Salcedo, Joshua P Fricks, Anjna Kalya and 1 more

Open access · goldAbstract read
In one paragraph

Article in Aging and disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.6field-weighted citation impact, top 8% of its field
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

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.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 12 citations in OpenAlex.

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  7. Ang II-mediated effects on BBB integrity in psychiatric and neurological disorders.Progress in neuro-psychopharmacology & biological psychiatry · 2026
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  11. A novel composite biomarker score for the identification of cognitive impairment in patients with heart failure: a pilot study.Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals · 2025
    Article
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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

11 authors at 1 institution in 1 country.

Christina Hoyer-KimuraDepartment of Physiology, The University of Arizona, Tucson, AZ 85724, USA.
Meredith HayDepartment of Physiology, The University of Arizona, Tucson, AZ 85724, USA.
John P KonhilasDepartment of Physiology, The University of Arizona, Tucson, AZ 85724, USA.
Helena W MorrisonCollege of Nursing, The University of Arizona, Tucson, AZ 85724, USA.
Methawasin MethajitDepartment of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ 85724, USA.
Joshua StromDepartment of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ 85724, USA.
Robin PoltDepartment of Chemistry and Biochemistry, The University of Arizona, Tucson, AZ 85724, USA.
Victoria SalcedoDepartment of Physiology, The University of Arizona, Tucson, AZ 85724, USA.
Joshua P FricksProNeurogen, Inc, Tucson, AZ, USA.
Anjna KalyaDepartment of Physiology, The University of Arizona, Tucson, AZ 85724, USA.
Paulo W PiresDepartment of Physiology, The University of Arizona, Tucson, AZ 85724, USA.
University of Arizona · US

Funding

IND Enabling Studies for a Novel Mas Receptor Agonist for Treatment of Cognitive Impairment in Patients at Risk for Alzheimer's Disease Related DementiaU01AG066623 · NIA · UNIVERSITY OF ARIZONA · PI HAY, MEREDITH, KONHILAS, JOHN P · 2020 to 2023
$8.0M
PNA5: A Novel Mas Receptor Agonist for Treatment of Cognitive Impairment in Patients at Risk for Vascular Dementia and Alzheimer's Disease Related Dementia: an FDA required Toxicology StudyU01AG082617 · NIA · UNIVERSITY OF ARIZONA · PI Meredith Hay, TODD W VANDERAH · 2023 to 2026
$8.0M
Role of Endothelial K+ Channels in Age-Related DementiaR01AG073230 · NIA · LOMA LINDA UNIVERSITY · PI Erik J. Behringer, Paulo W Pires · 2022 to 2026
$3.3M
NIA NIH HHS R01 AG073230NIA NIH HHS U01 AG066623NIA NIH HHS U01 AG082617
6 · The paper itself

Abstract

It is well established that decreased brain blood flow, increased reactive oxygen species production (ROS), and pro-inflammatory mechanisms accelerate neurodegenerative disease progressions, including vascular cognitive impairment and dementia (VCID). Previous studies in our laboratory have shown that our novel glycosylated Angiotensin-(1-7) Mas receptor agonist PNA5 reverses cognitive deficits, decreases ROS production, and inhibits inflammatory cytokine production in our preclinical mouse model of VCID that is induced by chronic heart failure (VCID-HF). In the present study, the effects of VCID-HF and treatment with PNA5 on microglia activation, blood-brain-barrier (BBB) integrity, and neurovascular coupling were assessed in our mouse model of VCID-HF. Three-month-old male C57BL/6J mice were subjected to myocardial infarction (MI) to induce heart failure for four weeks and then treated with subcutaneous injections of extended-release PNA5. Microglia activation, BBB permeability, cerebral perfusion, and neurovascular coupling were assessed. Results show that in our VCID-HF model, there was an increase in microglial activation and recruitment within the CA1 and CA3 regions of the hippocampus, a disruption in BBB integrity, and a decrease in neurovascular coupling. Treatment with PNA5 reversed these neuropathological effects of VCID-HF, suggesting that PNA5 may be an effective disease-modifying therapy to treat and prevent VCID. This study identifies potential mechanisms by which heart failure may induce VCID and highlights the possible mechanisms by which treatment with our novel glycosylated Angiotensin-(1-7) Mas receptor agonist, PNA5, may protect cognitive function in our model of VCID.

Indexed as

Blood-Brain BarrierDisease Models, AnimalMice, Inbred C57BLProto-Oncogene MasAnimalsCerebrovascular CirculationCognitive DysfunctionDementia, VascularHeart FailureMaleMiceMicrogliaPeptide FragmentsReceptors, G-Protein-CoupledPeptide FragmentsProto-Oncogene MasReceptors, G-Protein-Coupled

Identifiers

PMID37815905
PMCPMC11272189
OpenAlexW4387467518

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.