ArticleThe Journal of clinical investigation2022
KLF2 regulates neutrophil activation and thrombosis in cardiac hypertrophy and heart failure progression.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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
61 citing papers in PubMed, 91 citations in OpenAlex.
- Neutrophil extracellular traps in cardiovascular disease: Mechanisms and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- Associations of NLR, MLR, and (neutrophil + monocyte)/lymphocyte ratio with 30-day mortality in diabetic ICU patients with heart failure: A retrospective cohort study.International journal of cardiology. Heart & vasculature · 2026Article
- Multiple organ dysfunction syndrome: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Association between pan-immune-inflammation value and prognosis in lung cancer patients: a systematic review and meta-analysis.Translational cancer research · 2026Article
- Endothelial KLF4 depletion drives age-related neurovascular dysfunction and neuropsychiatric impairment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- GPR30-mediated NETs degradation via Trex1 in heart failure of aged female mice.Journal of translational medicine · 2026Article
- KLF2 Promotes Neutrophil Apoptosis in Mice with Myocardial ischemia-reperfusion Injury by Upregulating Notch1.Cell biochemistry and biophysics · 2026Article
- Heart failure in old hypertensive rats is accompanied by the increase of neutrophil extracellular traps and myeloid-derived suppressor cells.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Prognostic Value of Circulating NETosis Biomarkers in ST-Elevation Myocardial Infarction: Citrullinated Histone H3 Outperforms Cell-Free DNA and Nucleosomes.Journal of inflammation research · 2026Article
- Immune-Inflammatory markers and heart failure incidence and mortality: a population-based longitudinal study.Frontiers in cardiovascular medicine · 2026Article
- Machine learning prediction of postoperative pulmonary embolism: a multicenter external validation study highlighting inflammatory response and intraoperative hemodynamics.Frontiers in cardiovascular medicine · 2026Article
- Neutrophil Extracellular Traps in Heart Failure: From Pathophysiological Mechanisms to Therapeutic Targets.Journal of inflammation research · 2026Review
- Integrated analysis of cell-in-cell related genes and immune microenvironment in heart failure.Frontiers in cell and developmental biology · 2026Article
- Inhaled bovine lactoferrin modulates the p47phox-MPO-NETosis axis in acute lung injury: implications for bioengineered nanomedicine in respiratory infections.Frontiers in immunology · 2026Article
- Immune Cell-Mediated Inflammation in Heart Failure: Subset Heterogeneity and Targeted Therapy.International journal of general medicine · 2026Review
- Potential involvement of the KLF2-GPX4 axis in ferroptosis during S.aureus-induced osteomyelitis.Human genomics · 2025Article
- From Gut to Heart: Targeting Trimethylamine N-Oxide as a Novel Strategy in Heart Failure Management.Biomolecules · 2025Review
- Review
- Neutrophil Extracellular Traps in Cardiovascular Diseases: Pathological Roles and Therapeutic Implications.Biomolecules · 2025Review
- Establishment of the Diagnostic Signature of Ferroptosis Genes in Multiple Sclerosis.Biochemical genetics · 2025Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
18 authors at 4 institutions in 3 countries.
Funding
Abstract
It is widely recognized that inflammation plays a critical role in cardiac hypertrophy and heart failure. However, clinical trials targeting cytokines have shown equivocal effects, indicating the need for a deeper understanding of the precise role of inflammation and inflammatory cells in heart failure. Leukocytes from human subjects and a rodent model of heart failure were characterized by a marked reduction in expression of Klf2 mRNA. Using a mouse model of angiotensin II-induced nonischemic cardiac dysfunction, we showed that neutrophils played an essential role in the pathogenesis and progression of heart failure. Mechanistically, chronic angiotensin II infusion activated a neutrophil KLF2/NETosis pathway that triggered sporadic thrombosis in small myocardial vessels, leading to myocardial hypoxia, cell death, and hypertrophy. Conversely, targeting neutrophils, neutrophil extracellular traps (NETs), or thrombosis ameliorated these pathological changes and preserved cardiac dysfunction. KLF2 regulated neutrophil activation in response to angiotensin II at the molecular level, partly through crosstalk with HIF1 signaling. Taken together, our data implicate neutrophil-mediated immunothrombotic dysregulation as a critical pathogenic mechanism leading to cardiac hypertrophy and heart failure. This neutrophil KLF2-NETosis-thrombosis mechanism underlying chronic heart failure can be exploited for therapeutic gain by therapies targeting neutrophils, NETosis, or thrombosis.
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.