ArticleCirculation research2015
Macrophage Mitochondrial Energy Status Regulates Cholesterol Efflux and Is Enhanced by Anti-miR33 in Atherosclerosis.
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In one paragraph
Article in Circulation research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
114citing papers in PubMed, 1 pooled it
7.6field-weighted citation impact, top 2% of its field
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Who cites it
114 citing papers in PubMed, 1 synthesis or guideline pooled it, 179 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- ATP Inside and Out: Understanding Atherosclerosis Through Energy Metabolism and Purinergic Signaling.Journal of atherosclerosis and thrombosis · 2026Review
- Context-dependent regulation of endothelial inflammation and atherosclerosis by endothelial microRNA-33.Atherosclerosis · 2026Article
- The cell with many faces: lung macrophage plasticity and function in response to environmental and pathogenic insults.Physiological reviews · 2026Review
- PDK4 is critical for metabolic regulation and progesterone production in bovine granulosa cells†.Biology of reproduction · 2026Article
- A Conjugation Delivery System of Macrophages and Platelet Pharmacytes Promotes Regeneration After Spinal Cord Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Non-coding RNA-driven cardiovascular immunometabolic reprogramming: from inflammatory endotypes to therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- Bibliometric analysis of research hotspots and emerging trends in microRNAs and atherosclerosis (2007-2025).Frontiers in cardiovascular medicine · 2026Review
- The impact of macrophage metabolism on idiopathic pulmonary fibrosis development and treatment prospectives.Frontiers in immunology · 2026Review
- Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives.Journal of atherosclerosis and thrombosis · 2026Review
- Decoding the crosstalk: interplay between macrophage programmed cell death networks and cholesterol efflux.Frontiers in cardiovascular medicine · 2026Review
- Reframing macrophage polarization through cholesterol efflux: an organelle-coupled immunometabolic model.Frontiers in immunology · 2026Review
- MicroRNA 223 Enhances ABCA1 Protein Stability and Supports Efflux in Cholesterol-Burdened Macrophages.Cell biochemistry and biophysics · 2025Article
- Wogonin Attenuates Atherosclerosis via KLF11-Mediated Suppression of PPARα-YAP1-Driven Glycolysis and Enhancement of ABCA1/G1-Mediated Cholesterol Efflux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Perfluorinated compounds exposure and atherogenic risk characteristics in a high-fat diet condition: In vitro/in vivo models and population panel study.PNAS nexus · 2025Article
- Inhibiting MiR-33a-3p Expression Fails to Enhance ApoAI-Mediated Cholesterol Efflux in Pro-Inflammatory Endothelial Cells.Medicina (Kaunas, Lithuania) · 2025Article
- Metabolic Status and Expression Level of SREBP mRNA and Mir-33 Among Children Conceived by Assisted Reproductive Technology.International journal of genomics · 2025Article
- Article
- miR-33 deletion in hepatocytes attenuates MASLD-MASH-HCC progression.JCI insight · 2024Article
- Immunometabolism in atherosclerotic disorders.Nature cardiovascular research · 2024Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Denuja KarunakaranFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
A Brianne ThrushFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
My-Anh NguyenFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Laura RichardsFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Michele GeoffrionFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Ragunath SingaraveluFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Eleni RamphosFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Prakriti ShangariFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Mireille OuimetFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
John P PezackiFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Kathryn J MooreFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Ljubica PerisicFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Lars MaegdefesselFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Ulf HedinFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Mary-Ellen HarperFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden.
Katey J RaynerFrom the University of Ottawa Heart Institute, Ottawa, Ontario, Canada (D.K., M.-A.N., L.R., M.G., E.R., P.S., K.J.R.); Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada (A.B.T., M.-A.N., R.S., J.P.P., M.-E.H., K.J.R.); National Research Council of Canada, Ottawa, Ontario, Canada (R.S., J.P.P.); Marc and Ruti Bell Program for Vascular Biology and Disease, The Leon H. Charney Division of Cardiology, New York University School of Medicine (M.O., K.J.M.); and Department of Molecular Medicine and Surgery (L.P., U.H.) and Department of Medicine (L.M.), Karolinska Institute, Stockholm, Sweden. krayner@ottawaheart.ca.
Karolinska Institutet · SEUniversity of Ottawa · CANational Research Council Canada · CA
Funding
MicroRNAs as physiological and pathological regulators of cholesterol homeostasisR01HL108182 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MOORE, KATHRYN J · 2011 to 2015
$2.1MmiR-33 Pathway Inhibition for Improving HDL FunctionalityR01HL119047 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MOORE, KATHRYN J, RAYNER, KATEY · 2015 to 2018
$1.9MCanadian Institutes of Health Research MOP130365Canadian Institutes of Health Research OCN126572NHLBI NIH HHS R01 HL108182NHLBI NIH HHS R01 HL119047
Abstract
rationaleTherapeutically targeting macrophage reverse cholesterol transport is a promising approach to treat atherosclerosis. Macrophage energy metabolism can significantly influence macrophage phenotype, but how this is controlled in foam cells is not known. Bioinformatic pathway analysis predicts that miR-33 represses a cluster of genes controlling cellular energy metabolism that may be important in macrophage cholesterol efflux.
objectiveWe hypothesized that cellular energy status can influence cholesterol efflux from macrophages, and that miR-33 reduces cholesterol efflux via repression of mitochondrial energy metabolism pathways. METHODS AND
resultsIn this study, we demonstrated that macrophage cholesterol efflux is regulated by mitochondrial ATP production, and that miR-33 controls a network of genes that synchronize mitochondrial function. Inhibition of mitochondrial ATP synthase markedly reduces macrophage cholesterol efflux capacity, and anti-miR33 required fully functional mitochondria to enhance ABCA1-mediated cholesterol efflux. Specifically, anti-miR33 derepressed the novel target genes PGC-1α, PDK4, and SLC25A25 and boosted mitochondrial respiration and production of ATP. Treatment of atherosclerotic Apoe(-/-) mice with anti-miR33 oligonucleotides reduced aortic sinus lesion area compared with controls, despite no changes in high-density lipoprotein cholesterol or other circulating lipids. Expression of miR-33a/b was markedly increased in human carotid atherosclerotic plaques compared with normal arteries, and there was a concomitant decrease in mitochondrial regulatory genes PGC-1α, SLC25A25, NRF1, and TFAM, suggesting these genes are associated with advanced atherosclerosis in humans.
conclusionsThis study demonstrates that anti-miR33 therapy derepresses genes that enhance mitochondrial respiration and ATP production, which in conjunction with increased ABCA1 expression, works to promote macrophage cholesterol efflux and reduce atherosclerosis.
Indexed as
Adenosine TriphosphateAmino Acid Transport Systems, AcidicAnimalsApolipoproteins EAtherosclerosisBase SequenceCalcium-Binding ProteinsCell LineCholesterolGene Expression RegulationGenetic TherapyHEK293 CellsHumansMacrophagesMacrophages, PeritonealMiceAdenosine TriphosphateAmino Acid Transport Systems, AcidicApolipoproteins ECalcium-Binding ProteinsCholesterolMicroRNAsMirn33 microRNA, mouseMitochondrial Membrane Transport ProteinsOligonucleotides, AntisenseProtein Serine-Threonine KinasesSLC25A25 protein, humanTranscription FactorsatherosclerosischolesterolmacrophagesmicroRNA-33, mousemitochondria
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