Evidence map›Paper›PMID 39929946›Full record

ArticleScientific reports2025

Vericiguat prevents high glucose-mediated impaired vascular smooth muscle cGMP production and vasorelaxation.

David Polhemus, Diego Almodiel, Tarek Harb, Efthymios Ziogos, Nuria Amat-Codina, Mark Ranek, Lakshmi Santhanam, Gary Gerstenblith, Thorsten M Leucker

Abstract read
PubMed Full text at PMC Publisher
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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

David PolhemusDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Diego AlmodielDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Tarek HarbDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Efthymios ZiogosDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Nuria Amat-CodinaDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Mark RanekDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Lakshmi SanthanamDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Gary GerstenblithDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Thorsten M LeuckerDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. tleucke1@jhmi.edu.

Funding

Lysyl Oxidase Like 2: A Novel Target in Aging Associated Vascular StiffeningR01HL148112 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI SANTHANAM, LAKSHMI · 2020 to 2023
$1.9M
NHLBI NIH HHS R01 HL148112
6 · The paper itself

Abstract

Normal endothelial cell dependent vascular smooth muscle cell function is mediated by nitric oxide (NO), which stimulates soluble guanylyl cyclase (sGC) production of the second messenger cyclic guanosine monophosphate (cGMP) leading to increased protein kinase G (PKG) activity and vascular smooth muscle relaxation. NO bioavailability is impaired in high glucose (HG). We tested the hypothesis that the sGC sensitizer vericiguat reverses HG-mediated decreased sGC activity in two experimental models, human aortic vascular smooth muscle cells (HVSMCs) and isolated mouse aortic rings. HVSMCs were exposed to normal glucose (NG) or to HG with or without 1 μm vericiguat for 24 h and cGMP and PKG activity were measured. Murine aortic rings were incubated in NG or HG for 24 h. Following incubation, the aortic rings were placed in an organ chamber bath containing the same NG or HG concentration used during the incubation. Dose-response curves to increasing concentrations of acetylcholine (ACh) and sodium nitroprusside were constructed for four groups: control (NG), NG + vericiguat, HG, and HG + vericiguat. As compared with the results in the NG group, cGMP production and PKG activity were significantly impaired in the HG cells incubated without, but not in those incubated with, vericiguat. In isolated aortic rings, ACh-mediated relaxation was impaired following treatment with HG, but not when a HG group was treated with vericiguat. The findings suggest clinical studies are warranted to investigate the potential of sGC sensitization as a therapeutic intervention to improve vascular NO-cGMP signaling endothelium -dependent function that is impaired in HG settings such as diabetes and the metabolic syndrome.

Indexed as

Cyclic GMPGlucoseMuscle, Smooth, VascularPyrimidinesVasodilationAnimalsAortaCyclic GMP-Dependent Protein KinasesHumansMaleMiceMyocytes, Smooth MuscleNitric OxideSoluble Guanylyl CyclaseCyclic GMPCyclic GMP-Dependent Protein KinasesGlucoseNitric OxidePyrimidinesSoluble Guanylyl CyclasecGMPNitric oxideProtein kinase G activityVascular smooth muscle cell functionVericiguat

Identifiers

PMID39929946
PMCPMC11811225

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Registered trials

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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.