ArticleMolecular biology of the cell2013
Altered nitric oxide production mediates matrix-specific PAK2 and NF-κB activation by flow.
Article in Molecular biology of the cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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Who cites it
30 citing papers in PubMed, 53 citations in OpenAlex.
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- Spatial Mechano-Signaling Regulation of GTPases through Non-Degradative Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Different roles of endothelial cell-derived fibronectin and plasma fibronectin in endothelial dysfunction.Turkish journal of medical sciences · 2023Article
- Article
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- The iterative lipid impact on inflammation in atherosclerosis.Current opinion in lipidology · 2021Review
- Biochemical and mechanical signals in the lymphatic vasculature.Cellular and molecular life sciences : CMLS · 2021Review
- Sinner or Saint?: Nck Adaptor Proteins in Vascular Biology.Frontiers in cell and developmental biology · 2021Review
- Endothelial MT1-MMP targeting limits intussusceptive angiogenesis and colitis via TSP1/nitric oxide axis.EMBO molecular medicine · 2020Article
- Update of Immunosenescence in Cerebral Small Vessel Disease.Frontiers in immunology · 2020Review
- Integrin α5β1 regulates PP2A complex assembly through PDE4D in atherosclerosis.The Journal of clinical investigation · 2019Article
- Endothelial FN (Fibronectin) Deposition by α5β1 Integrins Drives Atherogenic Inflammation.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis.Journal of the American Heart Association · 2018Article
- Integrin signaling in atherosclerosis.Cellular and molecular life sciences : CMLS · 2017Review
- Interaction between integrin α5 and PDE4D regulates endothelial inflammatory signalling.Nature cell biology · 2016Article
- Blood Brothers: Hemodynamics and Cell-Matrix Interactions in Endothelial Function.Antioxidants & redox signaling · 2016Review
- The arterial microenvironment: the where and why of atherosclerosis.The Biochemical journal · 2016Review
- Role of biomechanical forces in the natural history of coronary atherosclerosis.Nature reviews. Cardiology · 2016Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Shear stress generated by distinct blood flow patterns modulates endothelial cell phenotype to spatially restrict atherosclerotic plaque development. Signaling through p21-activated kinase (PAK) mediates several of the deleterious effects of shear stress, including enhanced NF-κB activation and proinflammatory gene expression. Whereas shear stress activates PAK in endothelial cells on a fibronectin matrix, basement membrane proteins limit shear-induced PAK activation and inflammation through a protein kinase A-dependent pathway; however, the mechanisms underlying this regulation were unknown. We show that basement membrane proteins limit membrane recruitment of PAK2, the dominant isoform in endothelial cells, by blocking its interaction with the adaptor protein Nck. This uncoupling response requires protein kinase A-dependent nitric oxide production and subsequent PAK2 phosphorylation on Ser-20 in the Nck-binding domain. Of importance, shear stress does not stimulate nitric oxide production in endothelial cells on fibronectin, resulting in enhanced PAK activation, NF-κB phosphorylation, ICAM-1 expression, and monocyte adhesion. These data demonstrate that differential flow-induced nitric oxide production regulates matrix-specific PAK signaling and describe a novel mechanism of nitric oxide-dependent NF-κB inhibition.
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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.