Entry Name Fluid shear stress and atherosclerosis - Mirounga leonina (Southern elephant seal)
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 mlx05418 Fluid shear stress and atherosclerosis
Ortholog table Organism Mirounga leonina (Southern elephant seal) [GN:
mlx ]
Gene 118014942 LOW QUALITY PROTEIN: heat shock protein HSP 90-beta-like [KO:K04079 ]
118003137 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
118018328 TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973 ]
118012291 NFE2L2; nuclear factor erythroid 2-related factor 2 isoform X1 [KO:K05638 ]
118024368 PECAM1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471 ]
118004424 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
118020028 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
118006556 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
118016863 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
118019468 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
118006042 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
118023001 MEF2A; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260 ]
118016979 MEF2C; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454 ]
118013894 ARHGEF2; rho guanine nucleotide exchange factor 2 isoform X1 [KO:K12791 ]
118025746 TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158 ]
118008270 IL1R1; LOW QUALITY PROTEIN: interleukin-1 receptor type 1 [KO:K04386 ]
118027047 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
117999262 PDGFA; platelet-derived growth factor subunit A isoform X1 [KO:K04359 ]
117998664 PDGFB; platelet-derived growth factor subunit B isoform X1 [KO:K17386 ]
118018155 LOW QUALITY PROTEIN: ras-related C3 botulinum toxin substrate 1-like [KO:K04392 ]
117999338 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
117998715 RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860 ]
118024428 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
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 mlx04270 Vascular smooth muscle contraction
mlx04670 Leukocyte transendothelial migration
KO pathway LinkDB All DBs
