ArticleCirculation research2010
Matrix-specific protein kinase A signaling regulates p21-activated kinase activation by flow in endothelial cells.
Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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
35 citing papers in PubMed, 57 citations in OpenAlex.
- Shear Stress and Endothelial Mechanotransduction in Trauma Patients with Hemorrhagic Shock: Hidden Coagulopathy Pathways and Novel Therapeutic Strategies.International journal of molecular sciences · 2023Review
- Extracellular Matrix Remodeling in Vascular Disease: Defining Its Regulators and Pathological Influence.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- NPRC deletion mitigated atherosclerosis by inhibiting oxidative stress, inflammation and apoptosis in ApoE knockout mice.Signal transduction and targeted therapy · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- Different roles of endothelial cell-derived fibronectin and plasma fibronectin in endothelial dysfunction.Turkish journal of medical sciences · 2023Article
- 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
- siRNA nanoparticles targeting CaMKIIγ in lesional macrophages improve atherosclerotic plaque stability in mice.Science translational medicine · 2020Article
- Protein kinase A activity is regulated by actomyosin contractility during cell migration and is required for durotaxis.Molecular biology of the cell · 2020Article
- 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
- EphA2 stimulates VCAM-1 expression through calcium-dependent NFAT1 activity.Cellular signalling · 2018Article
- Inhibiting Integrin α5 Cytoplasmic Domain Signaling Reduces Atherosclerosis and Promotes Arteriogenesis.Journal of the American Heart Association · 2018Article
- Mechanosensing and fibrosis.The Journal of clinical investigation · 2018Review
- Integrin signaling in atherosclerosis.Cellular and molecular life sciences : CMLS · 2017Review
- cAMP-dependent protein kinase A (PKA) regulates angiogenesis by modulating tip cell behavior in a Notch-independent manner.Development (Cambridge, England) · 2016Article
- 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
- Endothelial fluid shear stress sensing in vascular health and disease.The Journal of clinical investigation · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleAtherosclerosis is initiated by blood flow patterns that activate inflammatory pathways in endothelial cells. Activation of inflammatory signaling by fluid shear stress is highly dependent on the composition of the subendothelial extracellular matrix. The basement membrane proteins laminin and collagen found in normal vessels suppress flow-induced p21 activated kinase (PAK) and nuclear factor (NF)-kappaB activation. By contrast, the provisional matrix proteins fibronectin and fibrinogen found in wounded or inflamed vessels support flow-induced PAK and NF-kappaB activation. PAK mediates both flow-induced permeability and matrix-specific activation of NF-kappaB.
objectiveTo elucidate the mechanisms regulating matrix-specific PAK activation. METHODS AND
resultsWe now show that matrix composition does not affect the upstream pathway by which flow activates PAK (integrin activation, Rac). Instead, basement membrane proteins enhance flow-induced protein kinase (PK)A activation, which suppresses PAK. Inhibiting PKA restored flow-induced PAK and NF-kappaB activation in cells on basement membrane proteins, whereas stimulating PKA inhibited flow-induced activation of inflammatory signaling in cells on fibronectin. PKA suppressed inflammatory signaling through PAK inhibition. Activating PKA by injection of the prostacyclin analog iloprost reduced PAK activation and inflammatory gene expression at sites of disturbed flow in vivo, whereas inhibiting PKA by PKA inhibitor (PKI) injection enhanced PAK activation and inflammatory gene expression. Inhibiting PAK prevented the enhancement of inflammatory gene expression by PKI.
conclusionsBasement membrane proteins inhibit inflammatory signaling in endothelial cells via PKA-dependent inhibition of PAK.
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.