Evidence map›Paper›PMID 34576086›Full record

ArticleInternational journal of molecular sciences2021

Cyclic GMP-Dependent Regulation of Vascular Tone and Blood Pressure Involves Cysteine-Rich LIM-Only Protein 4 (CRP4).

Natalie Längst, Julia Adler, Olga Schweigert, Felicia Kleusberg, Melanie Cruz Santos, Amelie Knauer, Matthias Sausbier, Tanja Zeller, Peter Ruth, Robert Lukowski

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. 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
0.4field-weighted citation impact, top 41% 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

2 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
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 at 2 institutions in 1 country.

Natalie LängstDepartment of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tuebingen, 72076 Tuebingen, Germany.
Julia AdlerDepartment of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tuebingen, 72076 Tuebingen, Germany.
Olga SchweigertCardiovascular Systems Medicine and Molecular Translation, University Center of Cardiovascular Science, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Felicia KleusbergDepartment of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tuebingen, 72076 Tuebingen, Germany.
Melanie Cruz SantosDepartment of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tuebingen, 72076 Tuebingen, Germany.
Amelie KnauerDepartment of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tuebingen, 72076 Tuebingen, Germany.
Matthias SausbierDepartment of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tuebingen, 72076 Tuebingen, Germany.
Tanja ZellerCardiovascular Systems Medicine and Molecular Translation, University Center of Cardiovascular Science, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
Peter RuthDepartment of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tuebingen, 72076 Tuebingen, Germany.
Robert LukowskiDepartment of Pharmacology, Toxicology and Clinical Pharmacy, Institute of Pharmacy, University of Tuebingen, 72076 Tuebingen, Germany.
University of Tübingen · DEUniversity Medical Center Hamburg-Eppendorf · DE

Funding

Deutsche Forschungsgemeinschaft LU 1490/3-2 and 335549539/GRK 2381German Center for Cardiovascular Research FKZ 81Z1710101 and FKZ 81Z0710102
6 · The paper itself

Abstract

The cysteine-rich LIM-only protein 4 (CRP4), a LIM-domain and zinc finger containing adapter protein, has been implicated as a downstream effector of the second messenger 3',5'-cyclic guanosine monophosphate (cGMP) pathway in multiple cell types, including vascular smooth muscle cells (VSMCs). VSMCs and nitric oxide (NO)-induced cGMP signaling through cGMP-dependent protein kinase type I (cGKI) play fundamental roles in the physiological regulation of vascular tone and arterial blood pressure (BP). However, it remains unclear whether the vasorelaxant actions attributed to the NO/cGMP axis require CRP4. This study uses mice with a targeted deletion of the CRP4 gene (CRP4 KO) to elucidate whether cGMP-elevating agents, which are well known for their vasorelaxant properties, affect vessel tone, and thus, BP through CRP4. Cinaciguat, a NO- and heme-independent activator of the NO-sensitive (soluble) guanylyl cyclase (NO-GC) and NO-releasing agents, relaxed both CRP4-proficient and -deficient aortic ring segments pre-contracted with prostaglandin F2α. However, the magnitude of relaxation was slightly, but significantly, increased in vessels lacking CRP4. Accordingly, CRP4 KO mice presented with hypotonia at baseline, as well as a greater drop in systolic BP in response to the acute administration of cinaciguat, sodium nitroprusside, and carbachol. Mechanistically, loss of CRP4 in VSMCs reduced the Ca

Indexed as

Blood PressureAnimalsBlood VesselsCalcium SignalingCyclic GMPCyclic GMP-Dependent Protein Kinase Type IFemaleLIM Domain ProteinsMaleMiceMice, KnockoutModels, BiologicalMuscle, Smooth, VascularMyocytes, Smooth MuscleNitric OxideNorepinephrineCyclic GMPCyclic GMP-Dependent Protein Kinase Type ILIM Domain ProteinsNitric OxideNorepinephrineSoluble Guanylyl CyclaseVasodilator Agentsblood pressure regulationCa2+-sensitivitycGKIcGMPCRP4myofilamentnitric oxideNO-GCPKGvascular toneVSMC

Identifiers

PMID34576086
PMCPMC8466836
OpenAlexW3198944924

What OpenQuestion holds

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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.