Evidence map›Paper›PMID 33119054›Full record

ArticleCardiovascular research2022

Genetic deletion of p66shc and/or cyclophilin D results in decreased pulmonary vascular tone.

Mareike Gierhardt, Oleg Pak, Akylbek Sydykov, Simone Kraut, Julia Schäffer, Claudia Garcia, Christine Veith, Esraa M Zeidan, Monika Brosien, Karin Quanz and 14 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

11 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 1 institution in 4 countries.

Mareike GierhardtExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Oleg PakExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Akylbek SydykovExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.ORCID 0000-0002-8122-7033
Simone KrautExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Julia SchäfferExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Claudia GarciaExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Christine VeithExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Esraa M ZeidanExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Monika BrosienExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Karin QuanzExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Azadeh EsfandiaryExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Alireza SarajiExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.ORCID 0000-0003-3053-8373
Stefan HadzicExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.ORCID 0000-0001-8459-2776
Baktybek KojonazarovExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Jochen WilhelmExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Hossein A GhofraniExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Ralph T SchermulyExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Werner SeegerExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Friedrich GrimmingerExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.
Christiane HerdenInstitute of Veterinary Pathology, Justus-Liebig University, Giessen, Germany.
Rainer SchulzInstitute of Physiology, Justus-Liebig University, Giessen, Germany.
Norbert WeissmannExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.ORCID 0000-0003-0827-0913
Jacqueline HegerInstitute of Physiology, Justus-Liebig University, Giessen, Germany.
Natascha SommerExcellence Cluster Cardio Pulmonary Institute (CPI), University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University, Giessen, Germany.ORCID 0000-0002-8915-7762
Justus-Liebig-Universität Gießen · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThe pulmonary vascular tone and hypoxia-induced alterations of the pulmonary vasculature may be regulated by the mitochondrial membrane permeability transition pore (mPTP) that controls mitochondrial calcium load and apoptosis. We thus investigated, if the mitochondrial proteins p66shc and cyclophilin D (CypD) that regulate mPTP opening affect the pulmonary vascular tone. METHODS AND

resultsMice deficient for p66shc (p66shc-/-), CypD (CypD-/-), or both proteins (p66shc/CypD-/-) exhibited decreased pulmonary vascular resistance (PVR) compared to wild-type mice determined in isolated lungs and in vivo. In contrast, systemic arterial pressure was only lower in CypD-/- mice. As cardiac function and pulmonary vascular remodelling did not differ between genotypes, we determined alterations of vascular contractility in isolated lungs and calcium handling in pulmonary arterial smooth muscle cells (PASMC) as underlying reason for decreased PVR. Potassium chloride (KCl)-induced pulmonary vasoconstriction and KCl-induced cytosolic calcium increase determined by Fura-2 were attenuated in all gene-deficient mice. In contrast, KCl-induced mitochondrial calcium increase determined by the genetically encoded Mito-Car-GECO and calcium retention capacity were increased only in CypD-/- and p66shc/CypD-/- mitochondria indicating that decreased mPTP opening affected KCl-induced intracellular calcium peaks in these cells. All mouse strains showed a similar pulmonary vascular response to chronic hypoxia, while acute hypoxic pulmonary vasoconstriction was decreased in gene-deficient mice indicating that CypD and p66shc regulate vascular contractility but not remodelling.

conclusionsWe conclude that p66shc specifically regulates the pulmonary vascular tone, while CypD also affects systemic pressure. However, only CypD acts via regulation of mPTP opening and mitochondrial calcium regulation.

Indexed as

Arterial PressureVasoconstrictionAnimalsCalciumCalcium SignalingCell ProliferationCells, CulturedDisease Models, AnimalGene DeletionHypertension, PulmonaryHypoxiaMiceMice, Inbred C57BLMice, KnockoutMitochondriaMitochondrial Permeability Transition PoreCalciumMitochondrial Permeability Transition PorePeptidyl-Prolyl Isomerase FShc1 protein, mouseSrc Homology 2 Domain-Containing, Transforming Protein 1CalciumCypDmitochondriap66shcPulmonary hypertension

Identifiers

PMID33119054
PMCPMC8752355
OpenAlexW3097125547

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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.