ArticleJCI insight2024
Activation of the IKK2/NF-κB pathway in VSMCs inhibits calcified vascular stiffness in CKD.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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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
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 3 citations in OpenAlex.
- Diagnostic and Therapeutic Roles of Extracellular Vesicles in Chronic Kidney Disease: A Systematic Review.Journal of extracellular vesicles · 2026Pooled it
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- Exosome-Mediated Systemic Signaling: Mechanisms, Disease Integration, and Translational Potential.Current issues in molecular biology · 2026Review
- Kidney-heart crosstalk: the extracellular vesicles connection.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Review
- TMEM174 Deficiency Reduces Longevity by Promoting Phosphate-Driven Vascular Calcification.Research square · 2026Article
- TMEM174 Deficiency Reduces Longevity by Promoting Phosphate-Driven Vascular Calcification.bioRxiv : the preprint server for biology · 2026Article
- Mechanisms of vascular calcification: cellular phenotype switching drives matrix remodeling and mineralized microenvironment formation.Frontiers in cardiovascular medicine · 2026Review
- Calciphylaxis diagnosis, management and future directions: a comprehensive update on behalf of the European Renal Association CKD-MBD Working Group.Clinical kidney journal · 2025Review
- Small Interfering RNA (siRNA) for Cardiorenal Disease: Mechanistic Insights from Preclinical and Clinical Studies.Journal of cardiovascular translational research · 2025Review
- Berberine and its derivatives: mechanisms of action in myocardial vascular endothelial injury - a review.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
IKK2/NF-κB pathway-mediated inflammation in vascular smooth muscle cells (VSMCs) has been proposed to be an etiologic factor in medial calcification and stiffness. However, the role of the IKK2/NF-κB pathway in medial calcification remains to be elucidated. In this study, we found that chronic kidney disease (CKD) induces inflammatory pathways through the local activation of the IKK2/NF-κB pathway in VMSCs associated with calcified vascular stiffness. Despite reducing the expression of inflammatory mediators, complete inhibition of the IKK2/NF-κB pathway in vitro and in vivo unexpectedly exacerbated vascular mineralization and stiffness. In contrast, activation of NF-κB by SMC-specific IκBα deficiency attenuated calcified vascular stiffness in CKD. Inhibition of the IKK2/NF-κB pathway induced cell death of VSMCs by reducing anti-cell death gene expression, whereas activation of NF-κB reduced CKD-dependent vascular cell death. In addition, increased calcification of extracellular vesicles through the inhibition of the IKK2/NF-κB pathway induced mineralization of VSMCs, which was significantly reduced by blocking cell death in vitro and in vivo. This study reveals that activation of the IKK2/NF-κB pathway in VSMCs plays a protective role in CKD-dependent calcified vascular stiffness by reducing the release of apoptotic calcifying extracellular vesicles.
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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.