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 K04079 molecular chaperone HtpG K09487 heat shock protein 90kDa beta K13242 nitric-oxide synthase, endothelial [EC:1.14.13.39] K06278 caveolin 1 K12958 caveolin 2 K12959 caveolin 3 K02183 calmodulin K08107 glypican 1 K06257 syndecan 1 K16336 syndecan 2 K16338 syndecan 4 K04973 transient receptor potential cation channel subfamily V member 4 K10456 kelch-like protein 19 K05638 nuclear factor erythroid 2-related factor 2 K00510 heme oxygenase 1 [EC:1.14.14.18] K00799 glutathione S-transferase [EC:2.5.1.18] K23790 glutathione S-transferase P [EC:2.5.1.18] K00355 NAD(P)H dehydrogenase (quinone) [EC:1.6.5.2] K14381 sequestosome 1 K03671 thioredoxin K12336 natriuretic peptide C K01940 argininosuccinate synthase [EC:6.3.4.5] K03907 thrombomodulin K01343 tissue plasminogen activator [EC:3.4.21.68] K06533 cadherin 5, type 2, VE-cadherin K05098 kinase insert domain protein receptor [EC:2.7.10.1] K02105 catenin beta 1 K07198 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31] K06471 platelet/endothelial cell adhesion molecule K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153] K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] K04463 mitogen-activated protein kinase kinase 5 [EC:2.7.12.2] K04464 mitogen-activated protein kinase 7 [EC:2.7.11.24] K09260 MADS-box transcription enhancer factor 2A K04454 MADS-box transcription enhancer factor 2C K17845 krueppel-like factor 2 K06476 integrin alpha 2B K06487 integrin alpha V K06493 integrin beta 3 K05704 tyrosine-protein kinase Src [EC:2.7.10.2] K05725 focal adhesion kinase 1 [EC:2.7.10.2] K12791 Rho guanine nucleotide exchange factor 2 K04513 Ras homolog gene family, member A K05692 actin beta/gamma 1 K21278 dual specificity protein phosphatase 1 [EC:3.1.3.16 3.1.3.48] K16864 microRNA 10a K03158 tumor necrosis factor receptor superfamily member 1A K04386 interleukin 1 receptor type I K04387 interleukin 1 receptor type II K04427 mitogen-activated protein kinase kinase kinase 7 [EC:2.7.11.25] K07210 inhibitor of nuclear factor kappa-B kinase subunit gamma K04467 inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10] K07209 inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10] K02580 nuclear factor NF-kappa-B p105 subunit K04735 transcription factor p65 K04426 mitogen-activated protein kinase kinase kinase 5 [EC:2.7.11.25] K04430 mitogen-activated protein kinase kinase 4 [EC:2.7.12.2] K04431 mitogen-activated protein kinase kinase 7 [EC:2.7.12.2] K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24] K20607 mitogen-activated protein kinase kinase 3 [EC:2.7.12.2] K04433 mitogen-activated protein kinase kinase 6 [EC:2.7.12.2] K04441 p38 MAP kinase [EC:2.7.11.24] K04379 proto-oncogene protein c-fos K04448 transcription factor AP-1 K01398 matrix metalloproteinase-2 (gelatinase A) [EC:3.4.24.24] K01403 matrix metalloproteinase-9 (gelatinase B) [EC:3.4.24.35] K01365 cathepsin L [EC:3.4.22.15] K14624 C-C motif chemokine 2 K06527 vascular cell adhesion molecule 1 K06490 intercellular adhesion molecule 1 K06494 selectin, endothelial cell K03156 tumor necrosis factor superfamily, member 2 K04383 interleukin 1 alpha K04519 interleukin 1 beta K04687 interferon gamma K04359 platelet-derived growth factor subunit A K17386 platelet-derived growth factor subunit B K16366 endothelin-1 K05448 vascular endothelial growth factor A K04662 bone morphogenetic protein 4 K04671 bone morphogenetic protein receptor type-2 [EC:2.7.11.30] K04670 activin receptor type-2A [EC:2.7.11.30] K13596 activin receptor type-2B [EC:2.7.11.30] K04675 activin receptor type-1 [EC:2.7.11.30] K04673 bone morphogenetic protein receptor type-1A [EC:2.7.11.30] K13578 bone morphogenetic protein receptor type-1B [EC:2.7.11.30] K08008 NADPH oxidase 1 K08009 cytochrome b-245, alpha polypeptide K08011 neutrophil cytosolic factor 1 K08010 neutrophil cytosolic factor 2 K04392 Ras-related C3 botulinum toxin substrate 1 K07860 Ras-related C3 botulinum toxin substrate 2 K07861 Ras-related C3 botulinum toxin substrate 3 K18952 atypical protein kinase C zeta type [EC:2.7.11.13] K16065 E3 SUMO-protein ligase PIAS4 [EC:2.3.2.27] K04451 tumor protein p53 K12160 small ubiquitin-related modifier K02161 apoptosis regulator Bcl-2 COMPOUND C00076 Calcium cation C00272 Tetrahydrobiopterin C00518 Hyaluronate C00533 Nitric oxide C00607 Chondroitin sulfate C00704 Superoxide C00925 Heparan sulfate C16845 Peroxynitrite REFERENCE PMID:21050140 AUTHORS Nigro P, Abe J, Berk BC TITLE Flow shear stress and atherosclerosis: a matter of site specificity. 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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 molecules ko04670 Leukocyte transendothelial migration ///