Evidence map›Paper›PMID 39885271›Full record

ArticleScientific reports2025

Muscarinic acetylcholine receptor 3 localized to primary endothelial cilia regulates blood pressure and cognition.

Hannah C Saternos, Kathleen V Forero, Mahmood A Meqdad, Raghad Buqaileh, Clare L Sunderman, Gillian Gallagher, William S Messer, Ashraf M Mohieldin, Claudio A Mucci, Sanjana Kumariya and 3 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Review
  6. Ciliary G-Protein Coupled Receptor Signaling in Polycystic Kidney Disease.International journal of molecular sciences · 2025
    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

13 authors.

Hannah C Saternos *Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Kathleen V Forero *Department of Pharmacology and Experimental Therapeutics; MS 1015, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Education Building; Room 282E, 3000 Arlington Ave, Toledo, OH, 43614, USA.
Mahmood A MeqdadDepartment of Pharmacology and Experimental Therapeutics; MS 1015, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Education Building; Room 282E, 3000 Arlington Ave, Toledo, OH, 43614, USA.
Raghad BuqailehDepartment of Pharmacology and Experimental Therapeutics; MS 1015, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Education Building; Room 282E, 3000 Arlington Ave, Toledo, OH, 43614, USA.
Clare L SundermanDepartment of Pharmacology and Experimental Therapeutics; MS 1015, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Education Building; Room 282E, 3000 Arlington Ave, Toledo, OH, 43614, USA.
Gillian GallagherDepartment of Pharmacology and Experimental Therapeutics; MS 1015, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Education Building; Room 282E, 3000 Arlington Ave, Toledo, OH, 43614, USA.
William S MesserDepartment of Pharmacology and Experimental Therapeutics; MS 1015, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Education Building; Room 282E, 3000 Arlington Ave, Toledo, OH, 43614, USA.
Ashraf M MohieldinMaster of Pharmaceutical Sciences Department, College of Graduate Studies, California Northstate University, Elk Grove, CA, USA.
Claudio A MucciDepartment of Biological Sciences, College of Natural Sciences and Mathematics, The University of Toledo, Toledo, OH, USA.
Sanjana KumariyaDepartment of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USA.
Islam A OsmanDepartment of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USA.
James P BurkettDepartment of Neurosciences, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, USA.
Wissam A AbouAlaiwiDepartment of Pharmacology and Experimental Therapeutics; MS 1015, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Health Education Building; Room 282E, 3000 Arlington Ave, Toledo, OH, 43614, USA. Wissam.Abou-Alaiwi@UToledo.Edu.

Funding

Program to Increase Diversity in Cardiovascular Health-Related Research(PRIDE-CVD)R25HL105446 · NHLBI · SUNY DOWNSTATE MEDICAL CENTER · PI Mohamed Boutjdir · 2010 to 2026
$5.9M
YAP1, neointima formation, and blood pressure regulationR00HL153896 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI OSMAN, ISLAM · 2023 to 2025
$747k
Role of muscarinic receptor anatgonist in primary cilia structureR15HL140523 · NHLBI · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI ABOUALAIWI, WISSAM · 2018 to 2020
$601k
Cerebrovascular endothelial cilia in the pathogenesis and therapy of Alzheimer's diseaseR03AG080418 · NIA · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · PI ABOUALAIWI, WISSAM · 2023 to 2024
$301k
Alzheimer's Association AARGD-NTF-22-972749,American Foundation of Pharmaceutical Education Gateway to Research AwardAmerican Heart Association (AHA) 19PRE34430055NHLBI NIH HHS R00 HL153896NHLBI NIH HHS R15 HL140523NHLBI NIH HHS R25 HL105446NIA NIH HHS 1R03AG080418-01NIA NIH HHS R03 AG080418NIH HHS R15HL140523, 3R15HL140523-01S1, 3R15HL140523-01S2, 3R15HL140523-01S3
6 · The paper itself

Abstract

We previously demonstrated that the inability of primary endothelial cilia to sense fluid shear stress can lead to nitric oxide (NO) deficiency and cause hypertension (HTN). Decreased biosynthesis of NO contributes to cerebral amyloid angiopathy in Alzheimer's disease (AD) patients through increased deposition of amyloid beta (Aβ). However, the molecular mechanisms underlying the pathogenesis of HTN and AD are incompletely understood. The objective of this study was to examine the pathophysiological roles of vascular primary cilia and muscarinic acetylcholine receptor 3 (CHRM3) in HTN and AD. We discovered, for the first time, that CHRM3 was localized to primary cilia of endothelial and cerebrovascular cells, and that CHRM3 expression was downregulated in cilialess cells. Moreover, CHRM3 activation enhanced cilia length and sensory function in terms of eNOS activation. To further examine the role of vascular CHRM3 in vivo, we showed that endothelial CHRM3 knockout was associated with increased BP and attenuated acetylcholine-mediated vascular relaxation. In addition, endothelial CHRM3 knockout resulted in altered fear behavior. This demonstrates the physiological significance of endothelial CHRM3 signaling and primary cilia-derived NO production as an important mechanism in the control of BP and cognition.

Indexed as

Blood PressureCiliaCognitionEndothelial CellsEndothelium, VascularReceptor, Muscarinic M3AcetylcholineAlzheimer DiseaseAnimalsHumansHypertensionMaleMiceMice, KnockoutNitric OxideNitric Oxide Synthase Type IIIAcetylcholineNitric OxideNitric Oxide Synthase Type IIIReceptor, Muscarinic M3

Identifiers

PMID39885271
PMCPMC11782538

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.