Pathway
Response of endothelial cells to shear stress
Vascular endothelial cells experience shear stress produced by the flow of blood across their apical surfaces. Different types of shear stress have been identified based on the type of flow and the response of the endothelial cells: low volume laminar flow, high volume laminar flow, and turbulent (disturbed, oscillatory) flow (reviewed in Davis et al. 2023, Rahaman et al. 2023, Lim and Harraz 2024). A key difference between the responses of cells to the different types of flow is the absence or presence of inflammation (reviewed in Davis et al. 2023, Wang et al. 2023). Whereas high volume laminar flow produces vasodilation and cytoskeletally based streamlining without inflammation, both turbulent flow and low volume laminar flow activate the inflammatory NF-kB and YAP1 pathways.
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All types of flow activate the mechanosensitive cation channel PIEZO1, resulting in an influx of calcium ions (Li et al. 2014, reviewed in Fang et al. 2021, Davis et al. 2023, Xiao et al. 2023). Calcium binds and activates the Calpain2 protease complex which acts on cytoskeletal proteins near the inner face of the plasma membrane, causing alterations to the morphology of the cell. In the case of high volume laminar flow, cells become ellipsoid with their long axes parallel with the flow of blood.
In addition to optimization of cell shape, high volume laminar flow activates AKT1 via ligand-independent KDR (VEGFR2) signaling, ATP-dependent P2RY2 signaling, and Adrenomedullin (ADM) signaling (Tzima et al. 2005, Wang et al. 2015, Iring et al. 2019, reviewed in Xiao et al. 2023). AKT1 and other kinases then phosphorylate NOS3 (eNOS), resulting in increased production of nitric oxide and vasodilation. High volume laminar flow is thus atheroprotective.
In contrast, turbulent flow activates signaling by integrin alpha5:beta1 (ITGA5:ITGB1) that causes the phosphodiesterase PDE4D5 to hydrolyze cAMP and the phosphatase PP2A to dephosphorylate and hence activate the transcription factor YAP1. YAP1 positively regulates expression of pro-inflammatory genes. Also during turbulent flow, Focal adhesion kinase (PTK2, FAK) is activated by phosphorylation and causes phosphorylation and nuclear translocation of the pro-inflammatory transcription factor complex NF-kB.
REACT:R-HSA-9860931Reactome
What the reference databases state
Statements
90 statements
90 statements · 1 reference database · Subject: Response of endothelial cells to shear stress · Sources: Reactome
- ABL1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ADCY1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ADCY2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ADCY3 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ADCY4 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ADCY5 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ADCY6 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ADCY7 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ADCY8 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ADCY9 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ADM participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- AKT1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
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- ANXA2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- CALCRL participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- CALM1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- CAPN2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- CAPNS1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- CAPNS2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- CDH5 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- CHUK participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- CTNNB1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- FLT4 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- FN1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- FYN participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNA11 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNAQ participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNB1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNB2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNB3 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNB4 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNB5 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNG10 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNG11 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNG12 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNG13 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNG2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNG3 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNG4 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNG5 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNG7 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNG8 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNGT1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- GNGT2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- IKBKB participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- IKBKE participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- IKBKG participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ITGA5 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ITGAV participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ITGB1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- ITGB3 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- KDR participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- MAPKAP1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- MLST8 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- MMP14 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- MTOR participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- NFKB1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- NFKBIA participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- NOS3 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- P2RY2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PANX1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PDPK1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PECAM1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PIEZO1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PIK3CA participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PIK3CB participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PIK3CD participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PIK3R2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PKN2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PPP2CA participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PPP2R1A participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PPP2R1B participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PPP2R2A participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PRKACA participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PRKACB participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PRKACG participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PRKAR1A participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PRKAR1B participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PRKAR2A participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PRKAR2B participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PRR5 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PTK2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- PTPN1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- RAMP2 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- RELA participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- RICTOR participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- STAT1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- TLN1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- TRPV4 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- VCL participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only
- YAP1 participates in Response of endothelial cells to shear stressProteinReactome R-HSA-9860931Inferred only