Evidence mapPaperPMID 41740187Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2026

Decreased AMP-kinase function in pulmonary artery smooth muscle cells contributes to pulmonary artery remodeling in persistent pulmonary hypertension of the newborn.

Emily A Mooers, Ujala Rana, Chintamani N Joshi, Adeleye J Afolayan, Ru-Jeng Teng, Girija G Konduri

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Article in American journal of physiology. Lung cellular and molecular physiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Emily A MooersDivision of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.ORCID 0009-0001-6677-6018
Ujala RanaDivision of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Chintamani N JoshiDivision of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.ORCID 0000-0002-8506-4139
Adeleye J AfolayanDivision of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.ORCID 0000-0001-9886-6694
Ru-Jeng TengDivision of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.ORCID 0000-0003-4321-2452
Girija G KonduriDivision of Neonatology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.ORCID 0000-0002-3602-1538

Funding

Role of Liver Kinase B1 in the decreased angiogenesis in bronchopulmonary dysplasiaR01HL174635 · MEDICAL COLLEGE OF WISCONSIN · 2025 to 2025
$645k
Advancing Healthier Wisconsin Endowment Program supportChildren's Hospital of Wisconsin Research Institute (Children's Research Institute)HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) 1R01HL136597-01HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) 1R01HL174635Medical College of Wisconsin (MCW) Pilot grant research affairs committeeNHLBI NIH HHS R01 HL136597NHLBI NIH HHS R01 HL174635
6 · The paper itself

Abstract

Pulmonary vascular remodeling contributes to persistent pulmonary hypertension of the newborn (PPHN); the mechanisms remain unknown. 5'-AMP-activated protein kinase (AMPK) is a critical regulator of energy balance and metabolism. We investigated the hypothesis that decreased AMPK function in pulmonary artery smooth muscle cells (PASMCs) leads to impaired mitochondrial capacity to perform oxidative phosphorylation and altered notch ligand expression, which together promote vascular remodeling in PPHN. Studies were performed in fetal lambs with PPHN induced by prenatal ductus arteriosus constriction and gestation-matched controls. For in vitro studies, PPHN PASMCs were treated with AMPK agonists, A769662 or metformin, and compared with untreated control and PPHN PASMCs. Expression of phosphorylated-AMPK (p-AMPK) and its downstream mediators, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial electron transport chain (ETC) complexes, differentiation markers, and notch ligands were assessed using immunoblotting in control and PPHN PASMCs. For in vivo studies, PPHN lambs were treated with metformin and were compared with untreated control and PPHN lambs. Lung sections from in vivo experiments were evaluated through immunofluorescence. Compared with controls, p-AMPK, PGC-1α, and ETC complexes were decreased in PPHN PASMCs and lung sections. PASMC differentiation marker, myosin heavy chain 11, was reduced in PPHN lung sections, whereas dedifferentiation marker, vimentin, was increased. Expression of Jag1 and Hey1 in Notch pathway was reduced in PPHN PASMCs and lung sections. A769662 and metformin increased the expression of PGC-1α, ETC complexes I and IV, Jag1, and Hey1 in PPHN PASMCs. Decreased AMPK function contributes to reduced mitochondrial oxidative phosphorylation capacity, less differentiated PASMCs, and imbalanced notch signaling, promoting remodeling in PPHN.

Indexed as

AMP-Activated Protein KinasesMuscle, Smooth, VascularMyocytes, Smooth MusclePersistent Fetal Circulation SyndromePulmonary ArteryVascular RemodelingAnimalsAnimals, NewbornBiphenyl CompoundsFemaleHypertension, PulmonaryMetforminMitochondriaPyronesReceptors, NotchSheep4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrileAMP-Activated Protein KinasesBiphenyl CompoundsMetforminPyronesReceptors, NotchThiophenesJagged1liver kinase B1mitochondrial functionnotch signalingproliferation

Identifiers

PMID41740187
PMCPMC13138608

What Socratic holds

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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 Socratic graph.