KEGG   PATHWAY: fca05418
Entry
fca05418                    Pathway                                
Name
Fluid shear stress and atherosclerosis - Felis catus (domestic cat)
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
fca05418  Fluid shear stress and atherosclerosis
fca05418

Organism
Felis catus (domestic cat) [GN:fca]
Gene
100049012  THBD; thrombomodulin [KO:K03907]
100127112  MCP-1; C-C motif chemokine 2 [KO:K14624]
100135774  PDGFB; platelet-derived growth factor subunit B isoform X4 [KO:K17386]
100142682  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
100142683  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100144392  ACTG1; actin, cytoplasmic 2 [KO:K05692]
100169963  GSTM3; glutathione S-transferase Mu 3 [KO:K00799] [EC:2.5.1.18]
100271864  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
100499544  AKT2; RAC-beta serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
101080443  [KO:K01365] [EC:3.4.22.15]
101080496  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
101080705  IL1R1; interleukin-1 receptor type 1 isoform X1 [KO:K04386]
101080760  MGST3; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
101080961  IL1R2; interleukin-1 receptor type 2 isoform X2 [KO:K04387]
101081453  CAV3; caveolin-3 [KO:K12959]
101081534  CALM2; calmodulin-2 [KO:K02183]
101082184  GSTP1; glutathione S-transferase P isoform X1 [KO:K23790]
101082249  HSP90B1; endoplasmin [KO:K09487]
101082489  BMPR1B; bone morphogenetic protein receptor type-1B isoform X3 [KO:K13578] [EC:2.7.11.30]
101082639  [KO:K01365] [EC:3.4.22.15]
101082912  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
101083114  [KO:K00799] [EC:2.5.1.18]
101083370  [KO:K00799] [EC:2.5.1.18]
101083623  [KO:K00799] [EC:2.5.1.18]
101084011  RHOA; transforming protein RhoA [KO:K04513]
101084185  MMP9; matrix metalloproteinase-9 [KO:K01403] [EC:3.4.24.35]
101084403  PECAM1; platelet endothelial cell adhesion molecule isoform X1 [KO:K06471]
101084501  CDH5; cadherin-5 isoform X2 [KO:K06533]
101084765  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101084793  [KO:K00799] [EC:2.5.1.18]
101084907  TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973]
101085041  GSTA4; glutathione S-transferase A4 [KO:K00799] [EC:2.5.1.18]
101085431  SQSTM1; sequestosome-1 isoform X2 [KO:K14381]
101085520  SELE; E-selectin [KO:K06494]
101085820  ITGAV; integrin alpha-V [KO:K06487]
101086087  ACVR2B; activin receptor type-2B isoform X1 [KO:K13596] [EC:2.7.11.30]
101086141  [KO:K12160]
101086376  NOX1; LOW QUALITY PROTEIN: NADPH oxidase 1 [KO:K08008]
101086432  MAP2K4; dual specificity mitogen-activated protein kinase kinase 4 isoform X1 [KO:K04430] [EC:2.7.12.2]
101086544  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
101086605  [KO:K01365] [EC:3.4.22.15]
101086824  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
101087196  ARHGEF2; rho guanine nucleotide exchange factor 2 isoform X2 [KO:K12791]
101087287  PDGFA; platelet-derived growth factor subunit A isoform X4 [KO:K04359]
101087771  SUMO3; small ubiquitin-related modifier 3 [KO:K12160]
101087851  PRKCZ; protein kinase C zeta type isoform X3 [KO:K18952] [EC:2.7.11.13]
101087880  [KO:K01365] [EC:3.4.22.15]
101087931  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101088712  NCF2; neutrophil cytosol factor 2 isoform X1 [KO:K08010]
101088865  VCAM1; vascular cell adhesion protein 1 isoform X1 [KO:K06527]
101089421  ICAM1; intercellular adhesion molecule 1 isoform X1 [KO:K06490]
101089548  BMPR1A; bone morphogenetic protein receptor type-1A [KO:K04673] [EC:2.7.11.30]
101089813  MAP2K6; dual specificity mitogen-activated protein kinase kinase 6 isoform X1 [KO:K04433] [EC:2.7.12.2]
101090141  GSTO2; glutathione S-transferase omega-2 isoform X1 [KO:K00799] [EC:2.5.1.18]
101090260  KDR; vascular endothelial growth factor receptor 2 [KO:K05098] [EC:2.7.10.1]
101090430  SDC4; syndecan-4 [KO:K16338]
101090655  TXN; thioredoxin [KO:K03671]
101090936  MGST2; microsomal glutathione S-transferase 2 isoform X1 [KO:K00799] [EC:2.5.1.18]
101091063  CALM3; calmodulin-3 [KO:K02183]
101091260  KEAP1; kelch-like ECH-associated protein 1 [KO:K10456]
101091298  ACVR1; activin receptor type-1 [KO:K04675] [EC:2.7.11.30]
101091310  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101091536  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
101091745  CYBA; cytochrome b-245 light chain [KO:K08009]
101091892  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101092159  ITGB3; integrin beta-3 [KO:K06493]
101092416  SDC2; syndecan-2 isoform X1 [KO:K16336]
101092550  [KO:K00799] [EC:2.5.1.18]
101092621  HMOX1; heme oxygenase 1 [KO:K00510] [EC:1.14.14.18]
101092798  [KO:K00799] [EC:2.5.1.18]
101092818  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
101093286  [KO:K02649]
101093416  DUSP1; dual specificity protein phosphatase 1 [KO:K21278] [EC:3.1.3.16 3.1.3.48]
101093586  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101094029  TXN2; thioredoxin, mitochondrial [KO:K03671]
101094122  GPC1; glypican-1 isoform X2 [KO:K08107]
101094221  SUMO2; small ubiquitin-related modifier 2 isoform X1 [KO:K12160]
101094274  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101094679  CALM1; calmodulin-1 [KO:K02183]
101094857  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
101095157  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
101095617  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
101095673  SUMO1; small ubiquitin-related modifier 1 [KO:K12160]
101095825  HSP90AB1; heat shock protein HSP 90-beta [KO:K04079]
101095885  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X3 [KO:K07198] [EC:2.7.11.31]
101095899  MAP3K7; mitogen-activated protein kinase kinase kinase 7 isoform X1 [KO:K04427] [EC:2.7.11.25]
101095952  PTK2; focal adhesion kinase 1 isoform X1 [KO:K05725] [EC:2.7.10.2]
101096000  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
101096136  MEF2C; myocyte-specific enhancer factor 2C isoform X1 [KO:K04454]
101096317  [KO:K00799] [EC:2.5.1.18]
101096338  BMPR2; bone morphogenetic protein receptor type-2 [KO:K04671] [EC:2.7.11.30]
101096463  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
101096604  RELA; transcription factor p65 [KO:K04735]
101096744  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
101097261  JUN; transcription factor AP-1 [KO:K04448]
101097342  CTNNB1; catenin beta-1 [KO:K02105]
101097351  GSTO1; glutathione S-transferase omega-1 isoform X2 [KO:K00799] [EC:2.5.1.18]
101097357  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
101097413  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101097525  ASS1; argininosuccinate synthase isoform X1 [KO:K01940] [EC:6.3.4.5]
101097703  [KO:K02183]
101097750  ACVR2A; activin receptor type-2A isoform X2 [KO:K04670] [EC:2.7.11.30]
101097827  NPPC; C-type natriuretic peptide [KO:K12336]
101097859  NQO1; NAD(P)H dehydrogenase [quinone] 1 isoform X1 [KO:K00355] [EC:1.6.5.2]
101098464  MEF2A; myocyte-specific enhancer factor 2A isoform X1 [KO:K09260]
101098507  ACTB; actin, cytoplasmic 1 [KO:K05692]
101098812  NFE2L2; nuclear factor erythroid 2-related factor 2 isoform X2 [KO:K05638]
101098838  MMP2; 72 kDa type IV collagenase [KO:K01398] [EC:3.4.24.24]
101098840  NCF1; neutrophil cytosol factor 1 isoform X1 [KO:K08011]
101099307  [KO:K02183]
101099565  MGST1; microsomal glutathione S-transferase 1 isoform X2 [KO:K00799] [EC:2.5.1.18]
101100031  PIAS4; E3 SUMO-protein ligase PIAS4 isoform X1 [KO:K16065] [EC:2.3.2.27]
101100214  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
101100299  PLAT; tissue-type plasminogen activator [KO:K01343] [EC:3.4.21.68]
101100311  BMP4; bone morphogenetic protein 4 isoform X2 [KO:K04662]
101100378  SRC; proto-oncogene tyrosine-protein kinase Src isoform X3 [KO:K05704] [EC:2.7.10.2]
101100725  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 isoform X1 [KO:K04463] [EC:2.7.12.2]
101100824  [KO:K00799] [EC:2.5.1.18]
101100930  ITGA2B; integrin alpha-IIb [KO:K06476]
101101037  [KO:K12160]
101101135  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101101277  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X3 [KO:K04392]
101101459  SDC1; syndecan-1 [KO:K06257]
101101463  MAPK10; mitogen-activated protein kinase 10 isoform X3 [KO:K04440] [EC:2.7.11.24]
102902667  [KO:K02183]
105259631  [KO:K01365] [EC:3.4.22.15]
105260786  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
111556320  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
111558264  KLF2; Krueppel-like factor 2 [KO:K17845]
111559122  [KO:K01365] [EC:3.4.22.15]
111559123  [KO:K01365] [EC:3.4.22.15]
111559124  [KO:K01365] [EC:3.4.22.15]
123379345  [KO:K12160]
123381292  [KO:K12160]
123381340  [KO:K12160]
123385094  [KO:K12160]
493667  CAV2; caveolin-2 [KO:K12958]
493668  CAV1; caveolin-1 [KO:K06278]
493755  TNF; tumor necrosis factor precursor [KO:K03156]
493845  VEGFA; vascular endothelial growth factor A precursor [KO:K05448]
493847  TP53; cellular tumor antigen p53 [KO:K04451]
493934  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
493935  FOS; proto-oncogene c-Fos [KO:K04379]
493944  IL1A; interleukin-1 alpha precursor [KO:K04383]
493957  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A precursor [KO:K03158]
493965  IFNG; interferon gamma precursor [KO:K04687]
494214  EDN1; endothelin-1 precursor [KO:K16366]
751112  PDP; procathepsin L isoform X1 [KO:K01365] [EC:3.4.22.15]
768274  IL1B; interleukin-1 beta [KO:K04519]
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.
  Journal
Antioxid Redox Signal 15:1405-14 (2011)
DOI:10.1089/ars.2010.3679
Reference
PMID:26597822
  Authors
McSweeney SR, Warabi E, Siow RC
  Title
Nrf2 as an Endothelial Mechanosensitive Transcription Factor: Going With the Flow.
  Journal
Hypertension 67:20-9 (2016)
DOI:10.1161/HYPERTENSIONAHA.115.06146
Reference
PMID:22076424
  Authors
Heo KS, Fujiwara K, Abe J
  Title
Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction.
  Journal
Circ J 75:2722-30 (2011)
DOI:10.1253/circj.CJ-11-1124
Reference
PMID:24573382
  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
Thromb Haemost 112:183-95 (2014)
DOI:10.1160/TH13-11-0908
Reference
PMID:21457103
  Authors
Noguchi N, Jo H
  Title
Redox going with vascular shear stress.
  Journal
Antioxid Redox Signal 15:1367-8 (2011)
DOI:10.1089/ars.2011.4011
Reference
PMID:25165867
  Authors
Li X, Yang Q, Wang Z, Wei D
  Title
Shear stress in atherosclerotic plaque determination.
  Journal
DNA Cell Biol 33:830-8 (2014)
DOI:10.1089/dna.2014.2480
Reference
PMID:17599600
  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
J Am Coll Cardiol 49:2379-93 (2007)
DOI:10.1016/j.jacc.2007.02.059
Reference
PMID:21733876
  Authors
Lu D, Kassab GS
  Title
Role of shear stress and stretch in vascular mechanobiology.
  Journal
J R Soc Interface 8:1379-85 (2011)
DOI:10.1098/rsif.2011.0177
Reference
PMID:27027326
  Authors
Givens C, Tzima E
  Title
Endothelial Mechanosignaling: Does One Sensor Fit All?
  Journal
Antioxid Redox Signal 25:373-88 (2016)
DOI:10.1089/ars.2015.6493
Reference
PMID:16765337
  Authors
Paravicini TM, Touyz RM
  Title
Redox signaling in hypertension.
  Journal
Cardiovasc Res 71:247-58 (2006)
DOI:10.1016/j.cardiores.2006.05.001
Reference
PMID:19151844
  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
PMID:24947523
  Authors
Bryan MT, Duckles H, Feng S, Hsiao ST, Kim HR, Serbanovic-Canic J, Evans PC
  Title
Mechanoresponsive networks controlling vascular inflammation.
  Journal
Arterioscler Thromb Vasc Biol 34:2199-205 (2014)
DOI:10.1161/ATVBAHA.114.303424
Reference
PMID:26822720
  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
Nat Rev Cardiol 13:210-20 (2016)
DOI:10.1038/nrcardio.2015.203
Reference
PMID:24876354
  Authors
Zhou J, Li YS, Chien S
  Title
Shear stress-initiated signaling and its regulation of endothelial function.
  Journal
Arterioscler Thromb Vasc Biol 34:2191-8 (2014)
DOI:10.1161/ATVBAHA.114.303422
Reference
PMID:23429585
  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
J Cardiovasc Pharmacol 61:461-70 (2013)
DOI:10.1097/FJC.0b013e31828c0933
Reference
PMID:20032497
  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
Blood 115:2533-42 (2010)
DOI:10.1182/blood-2009-06-228726
Reference
PMID:20353494
  Authors
Whyte JJ, Laughlin MH
  Title
The effects of acute and chronic exercise on the vasculature.
  Journal
Acta Physiol (Oxf) 199:441-50 (2010)
DOI:10.1111/j.1748-1716.2010.02127.x
Reference
PMID:25638487
  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
Nitric Oxide 45:20-6 (2015)
DOI:10.1016/j.niox.2015.01.006
Reference
PMID:15388638
  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
Circ Res 95:773-9 (2004)
DOI:10.1161/01.RES.0000145728.22878.45
Reference
PMID:23899566
  Authors
Hopkins PN
  Title
Molecular biology of atherosclerosis.
  Journal
Physiol Rev 93:1317-542 (2013)
DOI:10.1152/physrev.00004.2012
Reference
PMID:22003002
  Authors
Johnson BD, Mather KJ, Wallace JP
  Title
Mechanotransduction of shear in the endothelium: basic studies and clinical implications.
  Journal
Vasc Med 16:365-77 (2011)
DOI:10.1177/1358863X11422109
Reference
PMID:23555159
  Authors
Hu LS, George J, Wang JH
  Title
Current concepts on the role of nitric oxide in portal hypertension.
  Journal
World J Gastroenterol 19:1707-17 (2013)
DOI:10.3748/wjg.v19.i11.1707
Reference
PMID:23084990
  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
Curr Biol 22:2087-94 (2012)
DOI:10.1016/j.cub.2012.08.051
Reference
PMID:24190880
  Authors
Conway DE, Schwartz MA
  Title
Flow-dependent cellular mechanotransduction in atherosclerosis.
  Journal
J Cell Sci 126:5101-9 (2013)
DOI:10.1242/jcs.138313
Reference
PMID:26212910
  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
Am J Pathol 185:2575-89 (2015)
DOI:10.1016/j.ajpath.2015.05.013
Reference
PMID:20538799
  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
Blood 116:1971-9 (2010)
DOI:10.1182/blood-2010-02-269134
Related
pathway
fca04010  MAPK signaling pathway
fca04064  NF-kappa B signaling pathway
fca04151  PI3K-Akt signaling pathway
fca04210  Apoptosis
fca04270  Vascular smooth muscle contraction
fca04510  Focal adhesion
fca04514  Cell adhesion molecules
fca04670  Leukocyte transendothelial migration
KO pathway
ko05418   

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