ArticleNature communications2024
Aberrant mitochondrial DNA synthesis in macrophages exacerbates inflammation and atherosclerosis.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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35citing papers in PubMed, 1 pooled it
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Vascular Immunometabolism in Atherosclerosis: Emerging Roles of Glycometabolic Reprogramming in Immune and Vascular Cells.Cardiovascular drugs and therapy · 2026Pooled it
- Mitochondrial dysfunction and applications of mitochondrial-targeted delivery systems in atherosclerosis.Drug delivery · 2026Review
- Bone Marrow Macrophage STING Signaling is a Direct Nexus Linking Marrow Adipose Expansion to NADAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Spectral biophysical cytometry with nanosensors reveals remodelling of immune cells in atherosclerosis.Nature nanotechnology · 2026Article
- Macrophage RSAD2 Couples mtDNA Synthesis With a Self-Amplifying Inflammatory Circuit to Orchestrate Tissue Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- The Role of Inflammation and Immunity in Cardiovascular Disease: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer's disease pathogenesis.Neuron · 2026Article
- Mitochondrial homeostasis: the central hub governing the progression of atherosclerosis.Precision clinical medicine · 2026Review
- Magnetic Reprogramming of Macrophages Stimulates Phagocytosis of Breast Cancer Cells via a TRPC1-STING Inflammatory Axis.Smart medicine · 2026Article
- The cGAS-STING pathway in senescence and aging-related diseases: mechanisms and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- MSC-derived exosomes ameliorate systemic lupus erythematosus by reprogramming macrophage mitochondrial homeostasis via the CMPK2-cGAS-STING axis.Journal of nanobiotechnology · 2026Article
- Epigenetic control of microglial mitochondrial immunity by KAT7 drives Alzheimer's disease pathogenesis.bioRxiv : the preprint server for biology · 2026Article
- Unraveling key genes and mitochondrial-related mechanisms of atherosclerosis severity: explorations based on interpretable machine learning.BMC cardiovascular disorders · 2026Article
- A single-cell and spatial atlas of plaque macrophage states in human atherosclerosis.Frontiers in immunology · 2026Review
- Mitochondria-targeted nanotechnology in cardiovascular diseases: a review of recent advances.Regenerative biomaterials · 2026Review
- Bibliometric Analysis of Research Hotspots and Emerging Trends in Mitochondrial DNA and Atherosclerosis (2004-2025).Cardiology research and practice · 2026Review
- Eicosapentaenoic acid limits the more rapid oxidation of lipoprotein(a) compared with other apolipoprotein B particles.Cardiovascular research · 2025Article
- Self-DNA by Activating the CGAS-STING1 Pathway Contributes to the Pathogenesis of Atherosclerosis.Current atherosclerosis reports · 2025Review
- How interactions between oxidized DNA and the NLRP3 inflammasome fuel inflammatory disease.Trends in biochemical sciences · 2025Review
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Authors and funding
17 authors.
Niranjana Natarajan *Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Jonathan Florentin *Pittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Ebin JohnyPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Hanxi XiaoDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0003-3849-1696
Scott Patrick O'NeilPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Liqun LeiPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Jixing ShenPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Lee OhayonPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Aaron R JohnsonPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.ORCID 0000-0003-4512-2979
Krithika RaoPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Xiaoyun LiPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Yanwu ZhaoPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Yingze ZhangPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.ORCID 0000-0001-6947-2901
Sina TavakoliPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Sruti ShivaPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA.
Jishnu DasDepartment of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-5747-064X
Partha DuttaPittsburgh Heart, Lung, Blood, and Vascular Medicine Institute, Division of Cardiology, Department of Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA. duttapa@pitt.edu.ORCID 0000-0001-7456-1757
Funding
Mechanisms of Myocardial Infarction-induced insulin resistanceR01HL143967 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUTTA, PARTHA · 2018 to 2022
$2.6MCardioprotective role of Humanin in agingR01AG069399 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUTTA, PARTHA, MUZUMDAR, RADHIKA HIREN · 2021 to 2025
$2.3MThe role of microglia Nek6 in myocardial infarction-induced cognitive impairmentR01HL142629 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUTTA, PARTHA · 2020 to 2023
$2.3MThe role of SerpinB2 in insulin resistance and inflammationR01DK129339 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUTTA, PARTHA · 2022 to 2025
$1.7MA Molecular Imaging Approach to Immuno-Metabolic Characterization of Vessel Wall MacrophagesK08HL144911 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TAVAKOLI, SINA · 2019 to 2023
$813kBigfoot Spectral Cell SorterS10OD032265 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KANE, LAWRENCE P. · 2022 to 2022
$755kInvestigating the Role of Macrophages in Heart Failure with Preserved Ejection FractionR00HL157689 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Niranjana Natarajan · 2024 to 2026
$747kRequest for a Nikon A1 confocal microscopeS10OD019973 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WATKINS, SIMON C · 2015 to 2015
$358kInvestigating the Role of Macrophages in Heart Failure with Preserved Ejection FractionK99HL157689 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NATARAJAN, NIRANJANA · 2022 to 2023
$328kInvestigating the role of the complement system in cardiac regenerationF32HL146000 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NATARAJAN, NIRANJANA · 2019 to 2021
$200kNHLBI NIH HHS F32 HL146000NHLBI NIH HHS K08 HL144911NHLBI NIH HHS K99 HL157689NHLBI NIH HHS R00 HL157689NHLBI NIH HHS R01 HL142629NHLBI NIH HHS R01 HL143967NIA NIH HHS R01 AG069399NIDDK NIH HHS R01 DK129339NIH HHS S10 OD019973NIH HHS S10 OD032265
Abstract
There is a large body of evidence that cellular metabolism governs inflammation, and that inflammation contributes to the progression of atherosclerosis. However, whether mitochondrial DNA synthesis affects macrophage function and atherosclerosis pathology is not fully understood. Here we show, by transcriptomic analyzes of plaque macrophages, spatial single cell transcriptomics of atherosclerotic plaques, and functional experiments, that mitochondrial DNA (mtDNA) synthesis in atherosclerotic plaque macrophages are triggered by vascular cell adhesion molecule 1 (VCAM-1) under inflammatory conditions in both humans and mice. Mechanistically, VCAM-1 activates C/EBPα, which binds to the promoters of key mitochondrial biogenesis genes - Cmpk2 and Pgc1a. Increased CMPK2 and PGC-1α expression triggers mtDNA synthesis, which activates STING-mediated inflammation. Consistently, atherosclerosis and inflammation are less severe in Apoe
Indexed as
AtherosclerosisDNA, MitochondrialInflammationMacrophagesMembrane ProteinsPlaque, AtheroscleroticVascular Cell Adhesion Molecule-1AnimalsApolipoproteins EFemaleHumansMaleMiceMice, Inbred C57BLMice, Knockout, ApoEMitochondriaApolipoproteins EDNA, MitochondrialMembrane ProteinsPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPPARGC1A protein, humanSTING1 protein, humanSting1 protein, mouseSTING ProteinVascular Cell Adhesion Molecule-1
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