Evidence map›Paper›PMID 38844539›Full record

ArticlePediatric research2024

Aberrant PGC-1α signaling in a lamb model of persistent pulmonary hypertension of the newborn.

Emily A Mooers, Hollis M Johnson, Teresa Michalkiewicz, Ujala Rana, Chintamani Joshi, Adeleye J Afolayan, Ru-Jeng Teng, Girija G Konduri

Abstract read
In one paragraph

Article in Pediatric research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Mechanisms Underlying Altitude-Induced and Group 3 Pulmonary Hypertension.International journal of molecular sciences · 2026
    Review
  3. Restoration of pp60International journal of molecular sciences · 2025
    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

8 authors.

Emily A MooersInstitutional Affiliation (of all authors): Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin (MCW), Milwaukee, WI, USA. emooers@mcw.edu.ORCID 0000-0001-6207-4601
Hollis M JohnsonInstitutional Affiliation (of all authors): Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin (MCW), Milwaukee, WI, USA.
Teresa MichalkiewiczInstitutional Affiliation (of all authors): Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin (MCW), Milwaukee, WI, USA.
Ujala RanaInstitutional Affiliation (of all authors): Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin (MCW), Milwaukee, WI, USA.
Chintamani JoshiInstitutional Affiliation (of all authors): Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin (MCW), Milwaukee, WI, USA.
Adeleye J AfolayanInstitutional Affiliation (of all authors): Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin (MCW), Milwaukee, WI, USA.
Ru-Jeng TengInstitutional Affiliation (of all authors): Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin (MCW), Milwaukee, WI, USA.
Girija G KonduriInstitutional Affiliation (of all authors): Department of Pediatrics, Division of Neonatology, Medical College of Wisconsin (MCW), Milwaukee, WI, USA.

Funding

Role of Liver Kinase B1 in the decreased angiogenesis in bronchopulmonary dysplasiaR01HL174635 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI GIRIJA G. KONDURI · 2024 to 2026
$1.9M
AMP Kinase regulation in persistent pulmonary hypertension of the newbornR01HL136597 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI KONDURI, GIRIJA G. · 2018 to 2021
$1.5M
NHLBI NIH HHS R01 HL136597NHLBI NIH HHS R01 HL144519NHLBI NIH HHS R01 HL174635
6 · The paper itself

Abstract

backgroundPersistent Pulmonary Hypertension of the Newborn (PPHN) is characterized by elevated pulmonary vascular resistance (PVR), resulting in hypoxemia. Impaired angiogenesis contributes to high PVR. Pulmonary artery endothelial cells (PAECs) in PPHN exhibit decreased mitochondrial respiration and angiogenesis. We hypothesize that Peroxisome Proliferator-Activated Receptor Gamma Co-Activator-1α (PGC-1α) downregulation leads to reduced mitochondrial function and angiogenesis in PPHN.

methodsStudies were performed in PAECs isolated from fetal lambs with PPHN induced by ductus arteriosus constriction, with gestation-matched controls and in normal human umbilical vein endothelial cells (HUVECs). PGC-1α was knocked downed in control lamb PAECs and HUVECs and overexpressed in PPHN PAECs to investigate the effects on mitochondrial function and angiogenesis.

resultsPPHN PAECs had decreased PGC-1α expression compared to controls. PGC-1α knockdown in HUVECs led to reduced Nuclear Respiratory Factor-1 (NRF-1), Transcription Factor-A of Mitochondria (TFAM), and mitochondrial electron transport chain (ETC) complexes expression. PGC-1α knockdown in control PAECs led to decreased in vitro capillary tube formation, cell migration, and proliferation. PGC-1α upregulation in PPHN PAECs led to increased ETC complexes expression and improved tube formation, cell migration, and proliferation.

conclusionPGC-1α downregulation contributes to reduced mitochondrial oxidative phosphorylation through control of the ETC complexes, thereby affecting angiogenesis in PPHN. IMPACT: Reveals a novel mechanism for angiogenesis dysfunction in persistent pulmonary hypertension of the newborn (PPHN). Identifies a key mitochondrial transcription factor, Peroxisome Proliferator-Activated Receptor Gamma Co-Activator-1α (PGC-1α), as contributing to the altered adaptation and impaired angiogenesis function that characterizes PPHN through its regulation of mitochondrial function and oxidative phosphorylation. May provide translational significance as this mechanism offers a new therapeutic target in PPHN, and efforts to restore PGC-1α expression may improve postnatal transition in PPHN.

Indexed as

Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPersistent Fetal Circulation SyndromeSignal TransductionAnimalsAnimals, NewbornCell MovementCells, CulturedDisease Models, AnimalEndothelial CellsHumansHuman Umbilical Vein Endothelial CellsInfant, NewbornMitochondriaNeovascularization, PathologicNeovascularization, PhysiologicPulmonary ArteryPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPPARGC1A protein, human

Identifiers

PMID38844539
PMCPMC12101728

What Socratic holds

Textmetadata
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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.