Entry Name Fluid shear stress and atherosclerosis - Peromyscus leucopus (white-footed mouse)
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 pleu05418 Fluid shear stress and atherosclerosis
Organism Peromyscus leucopus (white-footed mouse) [GN:
pleu ]
Gene 114680645 Rac3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
114681336 Trpv4; transient receptor potential cation channel subfamily V member 4 isoform X1 [KO:K04973 ]
114684032 Pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
114686066 Map2k7; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431 ] [EC:2.7.12.2 ]
114688966 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
114690420 Pecam1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471 ]
114693559 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
114694276 Pdgfb; platelet-derived growth factor subunit B isoform X1 [KO:K17386 ]
114695216 Keap1; LOW QUALITY PROTEIN: kelch-like ECH-associated protein 1 [KO:K10456 ]
114695335 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
114695469 Mef2a; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260 ]
114697392 Mef2c; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454 ]
114700818 Nfe2l2; nuclear factor erythroid 2-related factor 2 isoform X1 [KO:K05638 ]
114703850 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
114705300 Vegfa; vascular endothelial growth factor A isoform X1 [KO:K05448 ]
114706924 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
114707535 Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
114708260 Calml6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183 ]
114708799 Tnfrsf1a; LOW QUALITY PROTEIN: tumor necrosis factor receptor superfamily member 1A [KO:K03158 ]
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 pleu04514 Cell adhesion molecule (CAM) interaction
pleu04670 Leukocyte transendothelial migration
KO pathway
