ArticleVascular pharmacology2022
Mitochondrial DNA and TLR9 activation contribute to SARS-CoV-2-induced endothelial cell damage.
Article in Vascular pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 2 syntheses or guidelines pooled it, 122 citations in OpenAlex.
- Host genetic factors modulating dengue virus: a systematic review of TLR polymorphisms.BMC infectious diseases · 2026Pooled it
- Mucosal immune response in biology, disease prevention and treatment.Signal transduction and targeted therapy · 2025Pooled it
- Oxidized mitochondrial DNA as a potential biomarker and mechanistic driver of autophagy-mitophagy dysregulation in pulmonary arterial hypertension: a narrative review.Molecular biology reports · 2026Review
- Mitochondrial Distress Signals at the Heart-Liver Interface: Molecular Links Between MASLD and Heart Failure.International journal of molecular sciences · 2026Review
- Defective RNA Polymerase III sensing of mitochondrial DNA in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Type I interferons in tuberculosis pathogenesis and prevention.Trends in microbiology · 2026Review
- Circulating Clues in Ménière's Disease: Elevated Cell-Free DNA and a Pro-Inflammatory Signature in Patients' Blood.International journal of molecular sciences · 2026Article
- TLR9 Inhibition Shortly After Mating Increases Fetal Resorption and Alters B- and T-Cell Costimulatory Phenotypes in an Abortion-Prone Mouse Model.International journal of molecular sciences · 2026Article
- Mechanisms and therapeutics of immunometabolic reprogramming driving macrophage-ECs interactions in sepsis-associated ARDS from the gut-lung axis perspective.Frontiers in immunology · 2026Review
- Innate immune activation and mitochondrial ROS induce acute and persistent cardiac conduction system dysfunction after COVID-19.JCI insight · 2025Article
- Mitochondrial dysfunction acts as a modulator of the immunometabolic route for activating the cytosolic DNA sensor pathway in triggering innate immunosurveillance.Journal of translational medicine · 2025Review
- Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.Microorganisms · 2025Review
- The role and mechanism of PGC-1α in oxLDL-induced ferroptosis of vascular endothelial cells.Atherosclerosis plus · 2025Article
- Deciphering TLR and JAK/STAT pathways: genetic variants and targeted therapies in COVID-19.Molecular biology reports · 2025Review
- SARS-CoV-2 nucleocapsid protein directly prevents cGAS-DNA recognition through competitive binding.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endothelial cell-released mitochondrial DNA promotes B cell differentiation and virus replication during severe fever with thrombocytopenia syndrome virus infection.Journal of virology · 2025Article
- Mitochondrial dysfunction in AMI: mechanisms and therapeutic perspectives.Journal of translational medicine · 2025Review
- Extracellular Vesicles Alter Trophoblast Function in Pregnancies Complicated by COVID-19.Journal of extracellular vesicles · 2025Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Interferon Regulatory Factor 3 Exacerbates the Severity of COVID-19 in Mice.Critical care explorations · 2025Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeMitochondria play a central role in the host response to viral infection and immunity, being key to antiviral signaling and exacerbating inflammatory processes. Mitochondria and Toll-like receptor (TLR) have been suggested as potential targets in SARS-CoV-2 infection. However, the involvement of TLR9 in SARS-Cov-2-induced endothelial dysfunction and potential contribution to cardiovascular complications in COVID-19 have not been demonstrated. This study determined whether infection of endothelial cells by SARS-CoV-2 affects mitochondrial function and induces mitochondrial DNA (mtDNA) release. We also questioned whether TLR9 signaling mediates the inflammatory responses induced by SARS-CoV-2 in endothelial cells. EXPERIMENTAL APPROACH: Human umbilical vein endothelial cells (HUVECs) were infected by SARS-CoV-2 and immunofluorescence was used to confirm the infection. Mitochondrial function was analyzed by specific probes and mtDNA levels by real-time polymerase chain reaction (RT-PCR). Inflammatory markers were measured by ELISA, protein expression by western blot, intracellular calcium (Ca KEY
resultsSARS-CoV-2 infected HUVECs, which express ACE2 and TMPRSS2 proteins, and promoted mitochondrial dysfunction, i.e. it increased mitochondria-derived superoxide anion, mitochondrial membrane potential, and mtDNA release, leading to activation of TLR9 and NF-kB, and release of cytokines. SARS-CoV-2 also decreased nitric oxide synthase (eNOS) expression and inhibited Ca CONCLUSION AND APPLICATIONS: SARS-CoV-2 infection impairs mitochondrial function and activates TLR9 signaling in endothelial cells. TLR9 triggers inflammatory responses that lead to endothelial cell dysfunction, potentially contributing to the severity of symptoms in COVID-19. Targeting mitochondrial metabolic pathways may help to define novel therapeutic strategies for COVID-19.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.