Evidence map›Paper›PMID 41163035›Full record

ArticleCell communication and signaling : CCS2025

eNAMPT/TLR4 signaling drives PAH cellular phenotypic switching and lung vascular remodeling.

Mohamed Ahmed, Shaira L Kee, Nahla Zaghloul, Nancy G Casanova, Marisela Rodriguez, Carrie L Kempf, Sara M Camp, Jin H Song, Saad Sammani, Akash Gupta and 8 more

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In one paragraph

Article in Cell communication and signaling : CCS, 2025. 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

What it found

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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

18 authors.

Mohamed Ahmed *Department of Pediatrics, Division of Neonatology, University of Florida College of Medicine, Gainesville, FL, USA.
Shaira L Kee *Department of Epidemiology, University of Florida College of Public Health, Gainesville, FL, USA.
Nahla ZaghloulDepartment of Pediatrics, Division of Neonatology, University of Florida College of Medicine, Gainesville, FL, USA.
Nancy G CasanovaCenter for Inflammation Science and Systems Medicine, University of Florida Scripps Research Institute, Jupiter, FL, 33458, USA.
Marisela RodriguezCenter for Inflammation Science and Systems Medicine, University of Florida Scripps Research Institute, Jupiter, FL, 33458, USA.
Carrie L KempfCenter for Inflammation Science and Systems Medicine, University of Florida Scripps Research Institute, Jupiter, FL, 33458, USA.
Sara M CampCenter for Inflammation Science and Systems Medicine, University of Florida Scripps Research Institute, Jupiter, FL, 33458, USA.
Jin H SongCenter for Inflammation Science and Systems Medicine, University of Florida Scripps Research Institute, Jupiter, FL, 33458, USA.
Saad SammaniDepartment of Medicine, University of Arizona Health Sciences, Tucson, AZ, USA.
Akash GuptaDepartment of Medicine, University of Arizona Health Sciences, Tucson, AZ, USA.
Andrew J BryantDepartment of Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
Aikseng OoiCenter for Inflammation Science and Systems Medicine, University of Florida Scripps Research Institute, Jupiter, FL, 33458, USA.
Ankit A DesaiDepartment of Medicine, Indiana University, Indianapolis, IN, USA.
Ayako MakinoCenter for Inflammation Science and Systems Medicine, University of Florida Scripps Research Institute, Jupiter, FL, 33458, USA.
Jason X-J YuanCenter for Inflammation Science and Systems Medicine, University of Florida Scripps Research Institute, Jupiter, FL, 33458, USA.
Panayiotis V BenosDepartment of Epidemiology, University of Florida College of Public Health, Gainesville, FL, USA.
Zhiyu DaiDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Joe G N GarciaCenter for Inflammation Science and Systems Medicine, University of Florida Scripps Research Institute, Jupiter, FL, 33458, USA. jgn.garcia@ufl.edu.

Funding

SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI George S Watts · 1994 to 2026
$36.7M
Structure-Function Analysis of nmMLCK in EC Barrier ResponsesP01HL126609 · NHLBI · UNIVERSITY OF FLORIDA · PI Joe G. N. Garcia · 2016 to 2026
$24.4M
National Biological Sample and Data Repository for PAHR24HL105333 · NHLBI · CINCINNATI CHILDRENS HOSP MED CTR · PI NICHOLS, WILLIAM C · 2012 to 2016
$10.1M
Genomic Analysis of Tissue and Cellular Heterogeneity in IPFR01HL127349 · NHLBI · YALE UNIVERSITY · PI BENOS, PANAGIOTIS V, KAMINSKI, NAFTALI · 2015 to 2025
$5.9M
Ion Channels and Membrane Receptors in Pulmonary Arterial HypertensionR35HL171538 · NHLBI · UNIVERSITY OF FLORIDA · PI Jason X J Yuan · 2024 to 2026
$3.8M
Novel Involvement of NAMPT and TLR4 in PAH Vascular RemodelingR01HL141387 · NHLBI · UNIVERSITY OF FLORIDA · PI Joe G. N. Garcia, Ayako Makino · 2019 to 2026
$3.8M
Novel alveolar mechanisms of hypoxemia in hepatopulmonary syndromeR01HL169509 · NHLBI · UNIVERSITY OF ARIZONA · PI Zhiyu Dai, MICHAEL B FALLON · 2023 to 2026
$3.0M
General Capillary to Arterial Endothelial Cell Transition in Pulmonary ArterialHypertensionR01HL170096 · NHLBI · WASHINGTON UNIVERSITY · PI Zhiyu Dai · 2023 to 2026
$2.9M
Role of Endothelial SOX17 Deficiency in the Pathogenesis of Pulmonary HypertensionR01HL158596 · NHLBI · WASHINGTON UNIVERSITY · PI Zhiyu Dai · 2022 to 2026
$2.3M
Fatty acid-binding proteins sustain endothelial glycolysis and arterial programming in pulmonary arterial hypertensionR01HL162794 · NHLBI · WASHINGTON UNIVERSITY · PI Zhiyu Dai · 2023 to 2026
$2.3M
Preclinical Development of a Novel eNAMPT-Neutralizing mAb for Pulmonary HypertensionR42HL164300 · NHLBI · AQUALUNG THERAPEUTICS CORP. · PI GARCIA, JOE G. N. · 2022 to 2024
$1.9M
NHLBI NIH HHS P01 HL126609NHLBI NIH HHS R01HL105333NHLBI NIH HHS R01 HL127349NHLBI NIH HHS R01HL127349NHLBI NIH HHS R01 HL141387NHLBI NIH HHS R01 HL158596NHLBI NIH HHS R01HL158596NHLBI NIH HHS R01 HL162794NHLBI NIH HHS R01 HL169509NHLBI NIH HHS R01 HL170096NHLBI NIH HHS R24 HL105333NHLBI NIH HHS R35 HL171538NHLBI NIH HHS R35HL171538NHLBI NIH HHS R42 HL164300NHLBI NIH HHS R42HL164300NIEHS NIH HHS P30 ES006694
6 · The paper itself

Abstract

backgroundThe attenuation of cellular phenotypic switchingdriving PAH vascular remodeling remains an unmet therapeutic need. As eNAMPT (nicotinamide phosphoribosyltransferase)/TLR4 signaling significantly contributes to PH pathobiology, an eNAMPT-neutralizing ALT-100 mAb was utilized to rescue monocrotaline (MCT) and hypoxia/Sugen (Hy/Su) preclinical PH rat models and to evaluate eNAMPT/TLR4 involvement in endothelial cell (EC), smooth muscle cell (SMC) and monocyte/macrophage phenotypic switching.

methodsMCT-PH or Hy/Su-PH rats received IgG or ALT-100 mAb (subQ, beginning week 4) with measurements of PH severity and lung tissue scRNAseq at day 42.

resultsPH severity indices (hemodynamic, histologic, vascular remodeling) were significantly attenuated in MCT-PH and Hy/Su-PH rats receiving ALT-100 mAb. scRNAseq studies revealed Hy/Su exposure increased populations of ECs undergoing EC-to-mesenchymal cell transition (EndMT), proliferating SMCs, and monocytes undergoing macrophage differentiation. Cellular phenotypic switching was ameliorated in Hy/Su-mAb rats.

conclusionsAutocrine/paracrine eNAMPT/TLR4 signaling contributes to accelerated cellular phenotypic switching, a druggable strategy to reverse vascular remodeling.

Indexed as

LungSignal TransductionToll-Like Receptor 4Vascular RemodelingAnimalsEndothelial CellsMaleMyocytes, Smooth MusclePhenotypeRatsRats, Sprague-DawleyTlr4 protein, ratToll-Like Receptor 4DAMPDEGEMTENAMPTEndMTMCTPAHTLR4

Identifiers

PMID41163035
PMCPMC12573901

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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.