Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells

Lv Y, Jiang Z, Zhou W, Yang H, Jin G, Wang D, Kong C, Qian Z, Gu Y, Chen S, Zhu L. Low-Shear Stress Promotes Atherosclerosis via Inducing Endothelial Cell Pyroptosis Mediated by IKKe/STAT1/NLRP3 Pathway. Inflammation. 2024 Feb 05;47(3):1053–66. doi: 10.1007/s10753-023-01960-w.; Rahaman SG, Mahanty M, Mukherjee P, Dutta B, Rahaman SO. Mechanosensing and Mechanosignal Transduction in Atherosclerosis. Curr Atheroscler Rep. 2023 Oct;25(10):711–21. doi: 10.1007/s11883-023-01139-6. PMID: 37615786.; Tamargo IA, Baek KI, Kim Y, Park C, Jo H. Flow-induced reprogramming of endothelial cells in atherosclerosis. Nat Rev Cardiol. 2023 May 24;20(11):738–53. doi: 10.1038/s41569-023-00883-1.; Wang X, Shen Y, Shang M, Liu X, Munn LL. Endothelial mechanobiology in atherosclerosis. Cardiovasc Res. 2023 Jul 06;119(8):1656–75. PMID: 37163659; PMCID: PMC10325702.; Zhang C, Zhou T, Chen Z, Yan M, Li B, Lv H, Wang C, Xiang S, Shi L, Zhu Y, Ai D. Coupling of Integrin a5 to Annexin A2 by Flow Drives Endothelial Activation. Circ Res. 2020 Sep 25;127(8):1074–90. doi: 10.1161/circresaha.120.316857. PMID: 32673515.; Li B, He J, Lv H, Liu Y, Lv X, Zhang C, Zhu Y, Ai D. c-Abl regulates YAPY357 phosphorylation to activate endothelial atherogenic responses to disturbed flow. J Clin Invest. 2019 Mar 01;129(3):1167–79. PMID: 30629551; PMCID: PMC6391101.; Albarrán-Juárez J, Iring A, Wang S, Joseph S, Grimm M, Strilic B, Wettschureck N, Althoff TF, Offermanns S. Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation. J Exp Med. 2018 Oct 01;215(10):2655–72. PMID: 30194266; PMCID: PMC6170174.; Yun S, Budatha M, Dahlman JE, Coon BG, Cameron RT, Langer R, Anderson DG, Baillie G, Schwartz MA. Interaction between integrin a5 and PDE4D regulates endothelial inflammatory signalling. Nat Cell Biol. 2016 Oct;18(10):1043–53. PMID: 27595237; PMCID: PMC5301150.; Dwyer SF, Gao L, Gelman IH. Identification of novel focal adhesion kinase substrates: role for FAK in NF?B signaling. Int J Biol Sci. 2015;11(4):404–10. PMID: 25798060; PMCID: PMC4366639.; Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science. 2010 Oct 01;330(6000):55–60. PMID: 20813920; PMCID: PMC3062430.; Miyazaki T, Honda K, Ohata H. m-Calpain antagonizes RhoA overactivation and endothelial barrier dysfunction under disturbed shear conditions. Cardiovasc Res. 2010 Feb 01;85(3):530–41. doi: 10.1093/cvr/cvp311. PMID: 19752040.; Miyazaki T, Honda K, Ohata H. Requirement of Ca2+ influx- and phosphatidylinositol 3-kinase-mediated m-calpain activity for shear stress-induced endothelial cell polarity. American Journal of Physiology-Cell Physiology. 2007 Oct;293(4):C1216–25. doi: 10.1152/ajpcell.00083.2007.

Metabolites

Calcium cation

Formula: Ca (39.962591)

CAS ID: 14127-61-8

H2O

Formula: H2O (18.0105642)

CAS ID: 7732-18-5

Magnesium cation

Formula: Mg (23.98505)

CAS ID: 22537-22-0

Zinc cation

Formula: Zn (63.929145)

CAS ID: 23713-49-7

ATP(4-)

Formula: C10H12N5O13P3 (502.9644492)

CAS ID:

ADP(3-)

Formula: C10H12N5O10P2 (424.0059412)

CAS ID:



Enzyme

EC Number name full name note
2.7.10.2 non-specific protein-tyrosine kinase ATP:[protein]-L-tyrosine O-phosphotransferase (non-specific)
2.7.11.10 IkappaB kinase ATP:[IkappaB protein] phosphotransferase
3.1.3.16 protein-serine/threonine phosphatase protein-serine/threonine-phosphate phosphohydrolase
3.1.4.53 3',5'-cyclic-AMP phosphodiesterase 3',5'-cyclic-AMP 5'-nucleotidohydrolase


Proteins

Protein ID name full name