ENTRY ko05418 Pathway 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 disease PATHWAY_MAP ko05418 Fluid shear stress and atherosclerosis ORTHOLOGY K00355 NQO1; NAD(P)H dehydrogenase (quinone) [EC:1.6.5.2] K00510 HMOX1; heme oxygenase 1 [EC:1.14.14.18] K00799 GST; glutathione S-transferase [EC:2.5.1.18] K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153] K01343 PLAT; tissue plasminogen activator [EC:3.4.21.68] K01365 CTSL; cathepsin L [EC:3.4.22.15] K01398 MMP2; matrix metalloproteinase-2 (gelatinase A) [EC:3.4.24.24] K01403 MMP9; matrix metalloproteinase-9 (gelatinase B) [EC:3.4.24.35] K01940 argG, ASS1; argininosuccinate synthase [EC:6.3.4.5] K02105 CTNNB1; catenin beta 1 K02161 BCL2; apoptosis regulator Bcl-2 K02183 CALM; calmodulin 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 K03671 TXN, trxA; thioredoxin 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] K04441 P38; p38 MAP 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 K04456 AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1] K04463 MAP2K5, MEK5; mitogen-activated protein kinase kinase 5 [EC:2.7.12.2] K04464 MAPK7; mitogen-activated protein kinase 7 [EC:2.7.11.24] 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 K04670 ACVR2A; activin receptor type-2A [EC:2.7.11.30] K04671 BMPR2; bone morphogenetic protein receptor type-2 [EC:2.7.11.30] K04673 BMPR1A, ALK3, CD292; bone morphogenetic protein receptor type-1A [EC:2.7.11.30] K04675 ACVR1, ALK2; activin receptor type-1 [EC:2.7.11.30] K04687 IFNG; interferon gamma 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 K05704 SRC; tyrosine-protein kinase Src [EC:2.7.10.2] K05725 PTK2, FAK; focal adhesion kinase 1 [EC:2.7.10.2] K06257 SDC1, CD138; syndecan 1 K06278 CAV1; caveolin 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 K08107 GPC1; glypican 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 K12958 CAV2; caveolin 2 K12959 CAV3; caveolin 3 K13242 NOS3; nitric-oxide synthase, endothelial [EC:1.14.13.39] K13578 BMPR1B, ALK6, CDw293; bone morphogenetic protein receptor type-1B [EC:2.7.11.30] K13596 ACVR2B; activin receptor type-2B [EC:2.7.11.30] K14381 SQSTM1; sequestosome 1 K14624 CCL2, MCP1; C-C motif chemokine 2 K16065 PIAS4; E3 SUMO-protein ligase PIAS4 [EC:2.3.2.27] K16336 SDC2, CD362; syndecan 2 K16338 SDC4; 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JOURNAL Blood 116:1971-9 (2010) DOI:10.1182/blood-2010-02-269134 REL_PATHWAY ko04010 MAPK signaling pathway ko04064 NF-kappa B signaling pathway ko04151 PI3K-Akt signaling pathway ko04210 Apoptosis ko04270 Vascular smooth muscle contraction ko04510 Focal adhesion ko04514 Cell adhesion molecule (CAM) interaction ko04670 Leukocyte transendothelial migration ///