ArticleCell reports. Medicine2024
A humanized monoclonal antibody targeting an ectonucleotidase rescues cardiac metabolism and heart function after myocardial infarction.
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Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10citing papers in PubMed
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Who cites it
10 citing papers in PubMed.
- Deciphering the role of cell-free extrachromosomal circular DNA in human heart failure.Human genomics · 2026Article
- Improvement of Cardiac Function by Polyclonal Antibodies Against CaInternational journal of molecular sciences · 2026Article
- A systems genetics approach to uncover mitochondrial drivers of heart failure reveals mitochondria-nuclear cross talk in genetically diverse mouse strains.bioRxiv : the preprint server for biology · 2025Article
- Self-DNA by Activating the CGAS-STING1 Pathway Contributes to the Pathogenesis of Atherosclerosis.Current atherosclerosis reports · 2025Review
- Genome-wide association study in chondrocalcinosis reveals ENPP1 as a candidate therapeutic target in calcium pyrophosphate deposition disease.Annals of the rheumatic diseases · 2025Article
- Krüppel like factor 7 regulates mitochondrial dynamics balance in myocardial infarction.Communications biology · 2025Article
- The CGAS-STING1 Pathway as a Mediator of Innate Immune Response in Cardiovascular Disease.JACC. Asia · 2025Review
- Retrospective Cardiac Gating with A Prototype Small-Animal X-ray Computed Tomograph.Journal of visualized experiments : JoVE · 2025Article
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- ENPP1/CD203a-targeting heavy-chain antibody reveals cell-specific expression on human immune cells.Cellular and molecular life sciences : CMLS · 2024Article
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Authors and funding
24 authors.
Shen LiDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; California Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Bo TaoDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; California Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Jijun WanDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; California Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Enca Montecino-RodriguezDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Ping WangDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; California Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Feiyang MaDepartment of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Baiming SunDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; California Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Yiqian GuDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Sivakumar RamadossDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; California Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Lianjiu SuDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; California Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Qihao SunDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; California Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Johanna Ten HoeveCalifornia Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA; UCLA Metabolomics Center, University of California, Los Angeles, Los Angeles, CA, USA; Crump Institute of Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Linsey StilesCalifornia Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA; Department of Medicine, Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jeffrey CollinsCalifornia Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA; Crump Institute of Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
R Michael van DamCalifornia Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA; Crump Institute of Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Mikayla TambolineCalifornia Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA; Crump Institute of Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Richard TaschereauCalifornia Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA; Crump Institute of Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Orian ShirihaiCalifornia Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA; Department of Medicine, Endocrinology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Douglas B KitchenDiscovery Services, Curia Global, Inc., Albany, NY 12212, USA.
Matteo PellegriniDepartment of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Thomas GraeberCalifornia Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA; UCLA Metabolomics Center, University of California, Los Angeles, Los Angeles, CA, USA; Crump Institute of Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Kenneth DorshkindDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Shili XuCalifornia Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA; Crump Institute of Molecular Imaging, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Arjun DebDivision of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Cardiovascular Theme, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA; Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA; California Nanosystems Institute, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: adeb@mednet.ucla.edu.
Funding
Metabolic and epigenetic reprogramming of vital organs in SARS-CoV-2 induced systemic toxicityR01DK132735 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARUMUGASWAMI, VAITHILINGARAJA, DEB, ARJUN · 2021 to 2023
$6.0MTargeting a ectonucleotidase in the heart with a monoclonal antibody to prevent post-infarct heart failureR01HL169217 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Arjun Deb · 2023 to 2026
$3.0MRole of GPNMB in cardiac remodelingR01HL152176 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2021 to 2024
$2.8MTargeting cardiac fibroblast-myocyte cross talk to enhance heart function after cardiac injuryR01HL149658 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2020 to 2023
$2.2MAdenine metabolism in cardiac repairR01HL171307 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Arjun Deb · 2024 to 2026
$2.2MRole of collagen heterogeneity in remodeling of acute and chronic heart scarsR01HL149687 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN, PELLEGRINI, MATTEO · 2020 to 2023
$2.0MRole of macrophages in regulating cardiac muscle metabolismR01HL176691 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Arjun Deb · 2025 to 2026
$1.5MIdentifying therapeutic strategies for the multisystem genetic disorder Pseudoxanthoma ElasticumR01AR075867 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DEB, ARJUN · 2020 to 2023
$1.4MSmall animal combined PET/CT systemS10OD026917 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHATZIIOANNOU, ARION XENOFON · 2020 to 2020
$750kNHLBI NIH HHS R01 HL149658NHLBI NIH HHS R01 HL149687NHLBI NIH HHS R01 HL152176NHLBI NIH HHS R01 HL169217NHLBI NIH HHS R01 HL171307NHLBI NIH HHS R01 HL176691NIAMS NIH HHS R01 AR075867NIDDK NIH HHS R01 DK132735NIH HHS S10 OD026917
Abstract
Myocardial infarction (MI) results in aberrant cardiac metabolism, but no therapeutics have been designed to target cardiac metabolism to enhance heart repair. We engineer a humanized monoclonal antibody against the ectonucleotidase ENPP1 (hENPP1mAb) that targets metabolic crosstalk in the infarcted heart. In mice expressing human ENPP1, systemic administration of hENPP1mAb metabolically reprograms myocytes and non-myocytes and leads to a significant rescue of post-MI heart dysfunction. Using metabolomics, single-nuclear transcriptomics, and cellular respiration studies, we show that the administration of the hENPP1mAb induces organ-wide metabolic and transcriptional reprogramming of the heart that enhances myocyte cellular respiration and decreases cell death and fibrosis in the infarcted heart. Biodistribution and safety studies showed specific organ-wide distribution with the antibody being well tolerated. In humanized animals, with drug clearance kinetics similar to humans, we demonstrate that a single "shot" of the hENPP1mAb after MI is sufficient to rescue cardiac dysfunction.
Indexed as
Antibodies, Monoclonal, HumanizedMyocardial InfarctionMyocardiumPhosphoric Diester HydrolasesPyrophosphatasesAnimalsHeartHumansMiceMyocytes, CardiacAntibodies, Monoclonal, Humanizedectonucleotide pyrophosphatase phosphodiesterase 1Phosphoric Diester HydrolasesPyrophosphatases
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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.