Evidence map›Paper›PMID 30621010›Full record

ReviewInternational journal of molecular sciences2019

New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease.

Andreas Daiber, Ning Xia, Sebastian Steven, Matthias Oelze, Alina Hanf, Swenja Kröller-Schön, Thomas Münzel, Huige Li

Registry-linked trialOpen access · goldAbstract readReview
In one paragraph

Review in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05798481 (A Pilot Pre-Phase 1 Clinical Trial to Study How Administering Sublingual Nitric Oxide Donor S-nitroso-N-acetylcysteine Affects the Systemic Blood Pressure in Healthy Human Volunteers.), which is not on this map. Cited by 151 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
151citing papers in PubMed, 1 pooled it
20.1field-weighted citation impact, top 1% 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.

NCT05798481 early_phase1completednot on this mapstarted 2024, after this paper: background citation

A Pilot Pre-Phase 1 Clinical Trial to Study How Administering Sublingual Nitric Oxide Donor S-nitroso-N-acetylcysteine Affects the Systemic Blood Pressure in Healthy Human Volunteers.

TypeinterventionalSponsorUniversity of Alabama at BirminghamRan2024 to 2025Enrolled14ConditionsHypertension, Cardiovascular DiseasesArmsMixture of Sodium Nitrite and N-acetylcysteine (NAC) crytals.
3 · Its place in the literature

Who cites it

151 citing papers in PubMed, 1 synthesis or guideline pooled it, 277 citations in OpenAlex.

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  8. Neurovascular interactions in the ageing heart.Nature reviews. Cardiology · 2026
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91 more citing papers are in PubMed but not listed here.

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

8 authors at 1 institution in 1 country.

Andreas DaiberCenter for Cardiology, Cardiology I-Laboratory of Molecular Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. daiber@uni-mainz.de.ORCID 0000-0002-2769-0094
Ning XiaDepartment of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. xianing@uni-mainz.de.
Sebastian StevenCenter for Cardiology, Cardiology I-Laboratory of Molecular Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. sebastiansteven@gmx.de.
Matthias OelzeCenter for Cardiology, Cardiology I-Laboratory of Molecular Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. matzeoelze@aol.com.
Alina HanfCenter for Cardiology, Cardiology I-Laboratory of Molecular Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. alina.hanf@gmx.net.
Swenja Kröller-SchönCenter for Cardiology, Cardiology I-Laboratory of Molecular Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. swenja.kroeller-schoen@gmx.de.
Thomas MünzelCenter for Cardiology, Cardiology I-Laboratory of Molecular Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. tmuenzel@uni-mainz.de.
Huige LiDepartment of Pharmacology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. huigeli@uni-mainz.de.ORCID 0000-0003-3458-7391
Johannes Gutenberg University Mainz · DE

Funding

Boehringer Ingelheim 749 Foundation "Novel and neglected cardiovascular risk factors"DZHK (German Center for Cardiovascular Research) Partner Site Rhine-MainFoundation Heart of Mainz continous
6 · The paper itself

Abstract

The Global Burden of Disease Study identified cardiovascular risk factors as leading causes of global deaths and life years lost. Endothelial dysfunction represents a pathomechanism that is associated with most of these risk factors and stressors, and represents an early (subclinical) marker/predictor of atherosclerosis. Oxidative stress is a trigger of endothelial dysfunction and it is a hall-mark of cardiovascular diseases and of the risk factors/stressors that are responsible for their initiation. Endothelial function is largely based on endothelial nitric oxide synthase (eNOS) function and activity. Likewise, oxidative stress can lead to the loss of eNOS activity or even "uncoupling" of the enzyme by adverse regulation of well-defined "redox switches" in eNOS itself or up-/down-stream signaling molecules. Of note, not only eNOS function and activity in the endothelium are essential for vascular integrity and homeostasis, but also eNOS in perivascular adipose tissue plays an important role for these processes. Accordingly, eNOS protein represents an attractive therapeutic target that, so far, was not pharmacologically exploited. With our present work, we want to provide an overview on recent advances and future therapeutic strategies that could be used to target eNOS activity and function in cardiovascular (and other) diseases, including life style changes and epigenetic modulations. We highlight the redox-regulatory mechanisms in eNOS function and up- and down-stream signaling pathways (e.g., tetrahydrobiopterin metabolism and soluble guanylyl cyclase/cGMP pathway) and their potential pharmacological exploitation.

Indexed as

AnimalsCardiovascular DiseasesEpigenesis, GeneticHumansModels, BiologicalNitric Oxide Synthase Type IIIOxidation-ReductionSocioeconomic FactorsNitric Oxide Synthase Type IIIcardiovascular diseaseendothelial dysfunctioneNOS uncouplingenvironmental stressorsinflammationlife style/behavioral health risk factorsoxidative stress

Identifiers

PMID30621010
PMCPMC6337296
OpenAlexW2908031581

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.