Entry Name Fluid shear stress and atherosclerosis
Description Shear stress represents the frictional force that the flow of blood exerts at the endothelial surface of the vessel wall and plays a central role in vascular biology and contributes to the progress of atherosclerosis. Sustained laminar flow with high shear stress upregulates expressions of endothelial cell (EC) genes and proteins that are protective against atherosclerosis. The key shear stress-induced transcription factors that govern the expression of these genes are Kruppel-like factor 2 (KLF2) and nuclear factor erythroid 2-like 2 (Nrf2). On the other hand, disturbed flow with associated reciprocating, low shear stress generally upregulates the EC genes and proteins that promote oxidative and inflammatory states in the artery wall, resulting in atherogenesis. Important transcriptional events that reflect this condition of ECs in disturbed flow include the activation of activator protein 1 (AP-1) and nuclear factor kappaB (NF-kappaB).
Class Human Diseases; Cardiovascular diseaseBRITE hierarchy
Pathway map ko05418 Fluid shear stress and atherosclerosis
Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02161 BCL2; apoptosis regulator Bcl-2
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K03158 TNFRSF1A, TNFR1, CD120a; tumor necrosis factor receptor superfamily member 1A
K03907 THBD, CD141; thrombomodulin
K04079 HSP90A, htpG; molecular chaperone HtpG
K04359 PDGFA; platelet-derived growth factor subunit A
K04379 FOS; proto-oncogene protein c-fos
K04383 IL1A; interleukin 1 alpha
K04386 IL1R1, CD121a; interleukin 1 receptor type I
K04387 IL1R2, CD121b; interleukin 1 receptor type II
K04392 RAC1; Ras-related C3 botulinum toxin substrate 1
K04426 MAP3K5, ASK1; mitogen-activated protein kinase kinase kinase 5 [EC:2.7.11.25 ]
K04427 MAP3K7, TAK1; mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25 ]
K04430 MAP2K4, MKK4; mitogen-activated protein kinase kinase 4 [EC:2.7.12.2 ]
K04431 MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2 ]
K04433 MAP2K6, MKK6; mitogen-activated protein kinase kinase 6 [EC:2.7.12.2 ]
K04440 JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K04448 JUN; transcription factor AP-1
K04451 TP53, P53; tumor protein p53
K04454 MEF2C; MADS-box transcription enhancer factor 2C
K04463 MAP2K5, MEK5; mitogen-activated protein kinase kinase 5 [EC:2.7.12.2 ]
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04513 RHOA; Ras homolog gene family, member A
K04519 IL1B; interleukin 1 beta
K04662 BMP4; bone morphogenetic protein 4
K04673 BMPR1A, ALK3, CD292; bone morphogenetic protein receptor type-1A [EC:2.7.11.30 ]
K04735 RELA; transcription factor p65
K04973 TRPV4; transient receptor potential cation channel subfamily V member 4
K05098 KDR, VEGFR2, CD309; kinase insert domain protein receptor [EC:2.7.10.1 ]
K05448 VEGFA; vascular endothelial growth factor A
K05638 NFE2L2, NRF2; nuclear factor erythroid 2-related factor 2
K05692 ACTB_G1; actin beta/gamma 1
K06257 SDC1, CD138; syndecan 1
K06471 PECAM1, CD31; platelet/endothelial cell adhesion molecule
K06476 ITGA2B, CD41; integrin alpha 2B
K06487 ITGAV, CD51; integrin alpha V
K06490 ICAM1, CD54; intercellular adhesion molecule 1
K06493 ITGB3, CD61; integrin beta 3
K06494 SELE, CD62E; selectin, endothelial cell
K06527 VCAM1, CD106; vascular cell adhesion molecule 1
K06533 CDH5, CD144; cadherin 5, type 2, VE-cadherin
K07198 PRKAA, AMPK; 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31 ]
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07860 RAC2; Ras-related C3 botulinum toxin substrate 2
K07861 RAC3; Ras-related C3 botulinum toxin substrate 3
K08008 NOX1, MOX1; NADPH oxidase 1
K08009 CYBA, P22PHOX; cytochrome b-245, alpha polypeptide
K08010 NCF2, P67PHOX; neutrophil cytosolic factor 2
K08011 NCF1, P47PHOX; neutrophil cytosolic factor 1
K09260 MEF2A; MADS-box transcription enhancer factor 2A
K09487 HSP90B, TRA1; heat shock protein 90kDa beta
K10456 KLHL19, KEAP1, INRF2; kelch-like protein 19
K12160 SUMO, SMT3; small ubiquitin-related modifier
K12336 NPPC; natriuretic peptide C
K12791 ARHGEF2, GEF-H1; Rho guanine nucleotide exchange factor 2
K13578 BMPR1B, ALK6, CDw293; bone morphogenetic protein receptor type-1B [EC:2.7.11.30 ]
K14624 CCL2, MCP1; C-C motif chemokine 2
K16336 SDC2, CD362; syndecan 2
K17386 PDGFB; platelet-derived growth factor subunit B
K17845 KLF2; krueppel-like factor 2
K23790 GSTP; glutathione S-transferase P
Compound Reference Authors Nigro P, Abe J, Berk BC
Title Flow shear stress and atherosclerosis: a matter of site specificity.
Journal Reference Authors McSweeney SR, Warabi E, Siow RC
Title Nrf2 as an Endothelial Mechanosensitive Transcription Factor: Going With the Flow.
Journal Reference Authors Heo KS, Fujiwara K, Abe J
Title Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction.
Journal Reference Authors Wild J, Soehnlein O, Dietel B, Urschel K, Garlichs CD, Cicha I
Title Rubbing salt into wounded endothelium: sodium potentiates proatherogenic effects of TNF-alpha under non-uniform shear stress.
Journal Reference Authors Noguchi N, Jo H
Title Redox going with vascular shear stress.
Journal Reference Authors Li X, Yang Q, Wang Z, Wei D
Title Shear stress in atherosclerotic plaque determination.
Journal Reference Authors Chatzizisis YS, Coskun AU, Jonas M, Edelman ER, Feldman CL, Stone PH
Title Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior.
Journal Reference Authors Lu D, Kassab GS
Title Role of shear stress and stretch in vascular mechanobiology.
Journal Reference Authors Givens C, Tzima E
Title Endothelial Mechanosignaling: Does One Sensor Fit All?
Journal Reference Authors Paravicini TM, Touyz RM
Title Redox signaling in hypertension.
Journal Reference Authors Boon RA, Horrevoets AJ
Title Key transcriptional regulators of the vasoprotective effects of shear stress.
Journal Hamostaseologie 29:39-40, 41-3 (2009)
Reference Authors Bryan MT, Duckles H, Feng S, Hsiao ST, Kim HR, Serbanovic-Canic J, Evans PC
Title Mechanoresponsive networks controlling vascular inflammation.
Journal Reference Authors Brown AJ, Teng Z, Evans PC, Gillard JH, Samady H, Bennett MR
Title Role of biomechanical forces in the natural history of coronary atherosclerosis.
Journal Reference Authors Zhou J, Li YS, Chien S
Title Shear stress-initiated signaling and its regulation of endothelial function.
Journal Reference Authors Liu HB, Zhang J, Xin SY, Liu C, Wang CY, Zhao D, Zhang ZR
Title Mechanosensitive properties in the endothelium and their roles in the regulation of endothelial function.
Journal Reference Authors Boon RA, Leyen TA, Fontijn RD, Fledderus JO, Baggen JM, Volger OL, van Nieuw Amerongen GP, Horrevoets AJ
Title KLF2-induced actin shear fibers control both alignment to flow and JNK signaling in vascular endothelium.
Journal Reference Authors Whyte JJ, Laughlin MH
Title The effects of acute and chronic exercise on the vasculature.
Journal Reference Authors Quillon A, Fromy B, Debret R
Title Endothelium microenvironment sensing leading to nitric oxide mediated vasodilation: a review of nervous and biomechanical signals.
Journal Reference Authors Sorescu GP, Song H, Tressel SL, Hwang J, Dikalov S, Smith DA, Boyd NL, Platt MO, Lassegue B, Griendling KK, Jo H
Title Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a nox1-based NADPH oxidase.
Journal Reference Authors Hopkins PN
Title Molecular biology of atherosclerosis.
Journal Reference Authors Johnson BD, Mather KJ, Wallace JP
Title Mechanotransduction of shear in the endothelium: basic studies and clinical implications.
Journal Reference Authors Hu LS, George J, Wang JH
Title Current concepts on the role of nitric oxide in portal hypertension.
Journal Reference Authors Collins C, Guilluy C, Welch C, O'Brien ET, Hahn K, Superfine R, Burridge K, Tzima E
Title Localized tensional forces on PECAM-1 elicit a global mechanotransduction response via the integrin-RhoA pathway.
Journal Reference Authors Conway DE, Schwartz MA
Title Flow-dependent cellular mechanotransduction in atherosclerosis.
Journal Reference Authors Chen J, Green J, Yurdagul A Jr, Albert P, McInnis MC, Orr AW
Title alphavbeta3 Integrins Mediate Flow-Induced NF-kappaB Activation, Proinflammatory Gene Expression, and Early Atherogenic Inflammation.
Journal Reference Authors Nigro P, Abe J, Woo CH, Satoh K, McClain C, O'Dell MR, Lee H, Lim JH, Li JD, Heo KS, Fujiwara K, Berk BC
Title PKCzeta decreases eNOS protein stability via inhibitory phosphorylation of ERK5.
Journal Related ko04064 NF-kappa B signaling pathway
ko04270 Vascular smooth muscle contraction
ko04670 Leukocyte transendothelial migration
