ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2021
miR-21 antagonism reprograms macrophage metabolism and abrogates chronic allograft vasculopathy.
Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Reprogramming macrophage metabolism for cardiovascular therapy: From molecular pathways to precision nanomedicine.Materials today. Bio · 2026Review
- Donor macrophage depletion permits posttransplant tolerance induction in a murine islet transplant model.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- MicroRNAs and their role in heart transplantation insights into rejection mechanisms: A narrative review.JHLT open · 2026Article
- Epigenetic regulation in transplant rejection and tolerance: mechanisms and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
- Macrophage metabolic reprogramming in organ transplantation: mechanisms, transplant outcomes, and therapeutic implications.Frontiers in cellular and infection microbiology · 2026Review
- Mitochondrial immunometabolism in sepsis: orchestrating macrophage polarization and dysfunction.European journal of medical research · 2025Review
- Best practices of heart transplantation in mice.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Review
- PTP Inhibition Improves the Macrophage Antitumor Immune Response and the Efficacy of Chemo- and Radiotherapy.Cancer immunology research · 2025Article
- Y4 RNA fragment alleviates myocardial injury in heart transplantation via SNRNP200 to enhance IL-10 mRNA splicing.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Molecular regulatory mechanisms and diagnostic potential of dendritic cell-derived exosomes in liver transplantation: from immune tolerance induction to translational challenges.Frontiers in immunology · 2025Review
- Role of macrophage in ocular neovascularization.Heliyon · 2024Review
- Plasma miR-150-5p in Renal Transplant Recipients with Acute Antibody-Mediated Rejection.Journal of clinical medicine · 2024Article
- TMEM219 regulates the transcription factor expression and proliferation of beta cells.Frontiers in endocrinology · 2024Article
- Innate immune cellular therapeutics in transplantation.Frontiers in transplantation · 2023Article
- New insights into maladaptive vascular responses to donor specific HLA antibodies in organ transplantation.Frontiers in transplantation · 2023Review
- Elucidation of endothelial progenitor cell dysfunction in diabetes by RNA sequencing and constructing lncRNA-miRNA-mRNA competing endogenous RNA network.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Bringing Clarity to the Murky Problem of Cardiac Allograft Vasculopathy.The American journal of pathology · 2022Article
- IL-4 polarized human macrophage exosomes control cardiometabolic inflammation and diabetes in obesity.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Review
- Liraglutide Attenuates Hepatic Ischemia-Reperfusion Injury by Modulating Macrophage Polarization.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
34 authors at 15 institutions in 4 countries.
Funding
Abstract
Despite much progress in improving graft outcome during cardiac transplantation, chronic allograft vasculopathy (CAV) remains an impediment to long-term graft survival. MicroRNAs (miRNAs) emerged as regulators of the immune response. Here, we aimed to examine the miRNA network involved in CAV. miRNA profiling of heart samples obtained from a murine model of CAV and from cardiac-transplanted patients with CAV demonstrated that miR-21 was most significantly expressed and was primarily localized to macrophages. Interestingly, macrophage depletion with clodronate did not significantly prolong allograft survival in mice, while conditional deletion of miR-21 in macrophages or the use of a specific miR-21 antagomir resulted in indefinite cardiac allograft survival and abrogated CAV. The immunophenotype, secretome, ability to phagocytose, migration, and antigen presentation of macrophages were unaffected by miR-21 targeting, while macrophage metabolism was reprogrammed, with a shift toward oxidative phosphorylation in naïve macrophages and with an inhibition of glycolysis in pro-inflammatory macrophages. The aforementioned effects resulted in an increase in M2-like macrophages, which could be reverted by the addition of L-arginine. RNA-seq analysis confirmed alterations in arginase-associated pathways associated with miR-21 antagonism. In conclusion, miR-21 is overexpressed in murine and human CAV, and its targeting delays CAV onset by reprogramming macrophages metabolism.
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