ArticleThe Journal of clinical investigation2020
Selective role of Nck1 in atherogenic inflammation and plaque formation.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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
17 citing papers in PubMed, 25 citations in OpenAlex.
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- Traditional Chinese Medicine Treating Dilated Cardiomyopathy: A Literature Review.International journal of general medicine · 2025Review
- EDIL3/Del-1 prevents aortic dissection through enhancing internalization and degradation of apoptotic vascular smooth muscle cells.Autophagy · 2024Article
- Plasma proteome association with coronary heart disease and carotid intima media thickness: results from the KORA F4 study.Cardiovascular diabetology · 2024Article
- Non-invasive modulation of meningeal lymphatics ameliorates ageing and Alzheimer's disease-associated pathology and cognition in mice.Nature communications · 2024Article
- Regulation of toll-like receptor (TLR) signaling pathways in atherosclerosis: from mechanisms to targeted therapeutics.Acta pharmacologica Sinica · 2023Review
- Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice.Cardiovascular diabetology · 2023Article
- Downregulation of MicroRNA-29-3p Following Percutaneous Coronary Intervention: An Implication of YY1/IRAK1 Pathway in the Post-Vascular Injury Inflammation.Acta Cardiologica Sinica · 2023Article
- Endothelial mechanobiology in atherosclerosis.Cardiovascular research · 2023Review
- The interleukin-1 receptor type-1 in disturbed flow-induced endothelial mesenchymal activation.Frontiers in cardiovascular medicine · 2023Article
- Interleukin Receptor Associated Kinase 1 Signaling and Its Association with Cardiovascular Diseases.Reviews in cardiovascular medicine · 2022Review
- Endothelial NCK2 promotes atherosclerosis progression in male but not femaleFrontiers in cardiovascular medicine · 2022Article
- Nck adaptors at a glance.Journal of cell science · 2021Article
- Coronary Artery Disease Genetics Enlightened by Genome-Wide Association Studies.JACC. Basic to translational science · 2021Review
- Sinner or Saint?: Nck Adaptor Proteins in Vascular Biology.Frontiers in cell and developmental biology · 2021Review
- Nck1 is a critical adaptor between proatherogenic blood flow, inflammation, and atherosclerosis.The Journal of clinical investigation · 2020Article
- Beyond Macrophages and T Cells: B Cells and Immunoglobulins Determine the Fate of the Atherosclerotic Plaque.International journal of molecular sciences · 2020Review
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
Although the Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) established the role of treating inflammation in atherosclerosis, our understanding of endothelial activation at atherosclerosis-prone sites remains limited. Disturbed flow at atheroprone regions primes plaque inflammation by enhancing endothelial NF-κB signaling. Herein, we demonstrate a role for the Nck adaptor proteins in disturbed flow-induced endothelial activation. Although highly similar, only Nck1 deletion, but not Nck2 deletion, limited flow-induced NF-κB activation and proinflammatory gene expression. Nck1-knockout mice showed reduced endothelial activation and inflammation in both models, disturbed flow- and high fat diet-induced atherosclerosis, whereas Nck2 deletion did not. Bone marrow chimeras confirmed that vascular Nck1, but not hematopoietic Nck1, mediated this effect. Domain-swap experiments and point mutations identified the Nck1 SH2 domain and the first SH3 domain as critical for flow-induced endothelial activation. We further characterized Nck1's proinflammatory role by identifying interleukin 1 type I receptor kinase-1 (IRAK-1) as a Nck1-selective binding partner, demonstrating that IRAK-1 activation by disturbed flow required Nck1 in vitro and in vivo, showing endothelial Nck1 and IRAK-1 staining in early human atherosclerosis, and demonstrating that disturbed flow-induced endothelial activation required IRAK-1. Taken together, our data reveal a hitherto unknown link between Nck1 and IRAK-1 in atherogenic inflammation.
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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 Socratic graph.