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Review

Flow pattern-dependent endothelial cell responses through transcriptional regulation

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Pages 1893-1901 | Received 02 Jun 2017, Accepted 30 Jul 2017, Published online: 08 Sep 2017

References

  • Hahn C, Schwartz MA. Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol. 2009;10:53-62. doi:10.1038/nrm2596. PMID:19197332
  • Zhou J, Li YS, Chien S. Shear stress-initiated signaling and its regulation of endothelial function. Arterioscler Thromb Vasc Biol. 2014;34:2191-2198. doi:10.1161/ATVBAHA.114.303422
  • Ando J, Yamamoto K. Effects of shear stress and stretch on endothelial function. Antioxid Redox Signal. 2011;15:1389-1403. doi:10.1089/ars.2010.3361. PMID:20854012
  • Freund JB, Goetz JG, Hill KL, Vermot J. Fluid flows and forces in development. functions, features and biophysical principles. Development. 2012;139:1229-1245. doi:10.1242/dev.073593. PMID:22395739
  • Chen Q, Jiang L, Li C, Hu D, Bu JW, Cai D, Du JL. Haemodynamics-driven developmental pruning of brain vasculature in zebrafish. PLoS Biol. 2012;10:e1001374. doi:10.1371/journal.pbio.1001374. PMID:22904685
  • Lucitti JL, Jones EA, Huang C, Chen J, Fraser SE, Dickinson ME. Vascular remodeling of the mouse yolk sac requires hemodynamic force. Development. 2007;134:3317-3326. doi:10.1242/dev.02883. PMID:17720695
  • Baeyens N, Schwartz MA. Biomechanics of vascular mechanosensation and remodeling. Mol Biol Cell. 2016;27:7-11. doi:10.1091/mbc.E14-11-1522. PMID:26715421
  • Ando J, Yamamoto K. Flow detection and calcium signalling in vascular endothelial cells. Cardiovasc Res. 2013;99:260-268. doi:10.1093/cvr/cvt084. PMID:23572234
  • Tarbell JM, Simon SI, Curry FR. Mechanosensing at the vascular interface. Annu Rev Biomed Eng. 2014;16:505-532. doi:10.1146/annurev-bioeng-071813-104908. PMID:24905872
  • Li J, Hou B, Tumova S, Muraki K, Bruns A, Ludlow MJ, Sedo A, Hyman AJ, McKeown L, Young RS, Yuldasheva NY, et al. Piezo1 integration of vascular architecture with physiological force. Nature. 2014;515:279-282. doi:10.1038/nature13701. PMID:25119035
  • Hierck BP, Van der Heiden K, Alkemade FE, Van de Pas S, Van Thienen JV, Groenendijk BC, Bax WH, Van der Laarse A, Deruiter MC, Horrevoets AJ, et al. Primary cilia sensitize endothelial cells for fluid shear stress. Dev Dyn 2008;237:725-735. doi:10.1002/dvdy.21472. PMID:18297727
  • Pahakis MY, Kosky JR, Dull RO, Tarbell JM. The role of endothelial glycocalyx components in mechanotransduction of fluid shear stress. Biochem Biophys Res Commun. 2007;355:228-233. doi:10.1016/j.bbrc.2007.01.137
  • Goetz JG, Steed E, Ferreira RR, Roth S, Ramspacher C, Boselli F, Charvin G, Liebling M, Wyart C, Schwab Y, et al. Endothelial cilia mediate low flow sensing during zebrafish vascular development. Cell Rep. 2014;6:799-808. doi:10.1016/j.celrep.2014.01.032
  • Tzima E, Irani-Tehrani M, Kiosses WB, Dejana E, Schultz DA, Engelhardt B, Cao G, DeLisser H, Schwartz MA. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature. 2005;437:426-431. doi:10.1038/nature03952. PMID:16163360
  • Li J, Hou B, Tumova S, Muraki K, Bruns A, Ludlow MJ, Sedo A, Hyman AJ, McKeown L, Young RS, et al. Piezo1 integration of vascular architecture with physiological force. Nature. 2014;515:279-282. doi:10.1038/nature13701. PMID:25119035
  • Helmke BP, Goldman RD, Davies PF. Rapid displacement of vimentin intermediate filaments in living endothelial cells exposed to flow. Circ Res. 2000;6:745-752. doi:10.1161/01.RES.86.7.745
  • Yu J, Bergaya S, Murata T, Alp IF, Bauer MP, Lin MI, Drab M, Kurzchalia TV, Stan RV, Sessa WC. Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels. J Clin Invest. 2006;116:1284-1291. doi:10.1172/JCI27100. PMID:16670769
  • Chiu JJ, Chien S. Effects of disturbed flow on vascular endothelium: Pathophysiological basis and clinical perspectives. Physiol Rev. 2011;91:327-387. doi:10.1152/physrev.00047.2009. PMID:21248169
  • Heo KS, Fujiwara K, Abe J. Shear stress and atherosclerosis. Mol Cells. 2014;37:435-440. doi:10.14348/molcells.2014.0078. PMID:24781409
  • Schober A, Nazari-Jahantigh M, Weber C. MicroRNA-mediated mechanisms of the cellular stress response in atherosclerosis. Nat Rev Cardiol. 2015;12:361-374. doi:10.1038/nrcardio.2015.38. PMID:25855604
  • Akimoto S, Mitsumata M, Sasaguri T, Yoshida Y. Laminar shear stress inhibits vascular endothelial cell proliferation by inducing cyclin-dependent kinase inhibitor p21(Sdi1/Cip1/Waf1). Circ Res. 2000;86:185-190. doi:10.1161/01.RES.86.2.185. PMID:10666414
  • Lin K, Hsu PP, Chen BP, Yuan S, Usami S, Shyy JY, Li YS, Chien S. Molecular mechanism of endothelial growth arrest by laminar shear stress. Proc Natl Acad Sci U S A. 2000;97:9385-9389. doi:10.1073/pnas.170282597. PMID:10920209
  • Bjorkerud S, Bondjers G. Endothelial integrity and viability in the aorta of the normal rabbit and rat as evaluated with dye exclusion tests and interference contrast microscopy. Atherosclerosis. 1972;15:285-300. doi:10.1016/0021-9150(72)90019-6. PMID:4115209
  • Hansson GK, Schwartz SM. Evidence for cell death in the vascular endothelium in vivo and in vitro. Am J Pathol. 1983;112:278-286. PMID:6351628
  • Sakao S, Taraseviciene-Stewart L, Lee JD, Wood K, Cool CD, Voelkel NF. Initial apoptosis is followed by increased proliferation of apoptosis-resistant endothelial cells. FASEB J. 2005;19:1178-1180. doi:10.1096/fj.04-3261fje. PMID:15897232
  • Tardy Y, Resnick N, Nagel T, Gimbrone MA, Jr., Dewey CF, Jr.. Shear stress gradients remodel endothelial monolayers in vitro via a cell proliferation-migration-loss cycle. Arterioscler Thromb Vasc Biol. 1997;17:3102-3106. doi:10.1161/01.ATV.17.11.3102. PMID:9409299
  • Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T, Cybulsky MI. The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci U S A. 2000;97:9052-9057. doi:10.1073/pnas.97.16.9052. PMID:10922059
  • Jongstra-Bilen J, Haidari M, Zhu SN, Chen M, Guha D, Cybulsky MI. Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J Exp Med. 2006;203:2073-2083. doi:10.1084/jem.20060245. PMID:16894012
  • Warboys CM, de Luca A, Amini N, Luong L, Duckles H, Hsiao S, White A, Biswas S, Khamis R, Chong CK, et al. Disturbed flow promotes endothelial senescence via a p53-dependent pathway. Arterioscler Thromb Vasc Biol. 2014;34:985-995. doi:10.1161/ATVBAHA.114.303415
  • Zarins CK, Giddens DP, Bharadvaj BK, Sottiurai VS, Mabon RF, Glagov S. Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ Res. 1983;53:502-514.
  • Atkins GB, Jain MK. Role of Kruppel-like transcription factors in endothelial biology. Circ Res. 2007;100:1686-1695. doi:10.1161/01.RES.0000267856.00713.0a
  • Parmar KM, Larman HB, Dai G, Zhang Y, Wang ET, Moorthy SN, Kratz JR, Lin Z, Jain MK, Gimbrone MA, Jr., et al. Integration of flow-dependent endothelial phenotypes by Kruppel-like factor 2. J Clin Invest. 2006;116:49-58. doi:10.1172/JCI24787. PMID:16341264
  • Le NT, Heo KS, Takei Y, Lee H, Woo CH, Chang E, McClain C, Hurley C, Wang X, Li F, et al. A crucial role for p90RSK-mediated reduction of ERK5 transcriptional activity in endothelial dysfunction and atherosclerosis. Circulation. 2013;127:486-499. doi:10.1161/CIRCULATIONAHA.112.116988
  • Ohnesorge N, Viemann D, Schmidt N, Czymai T, Spiering D, Schmolke M, Ludwig S, Roth J, Goebeler M, Schmidt M. Erk5 activation elicits a vasoprotective endothelial phenotype via induction of Kruppel-like factor 4 (KLF4). J Biol Chem. 2010;285:26199-26210. doi:10.1074/jbc.M110.103127. PMID:20551324
  • Dekker RJ, van Soest S, Fontijn RD, Salamanca S, de Groot PG, VanBavel E, Pannekoek H, Horrevoets AJ. Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung Kruppel-like factor (KLF2). Blood. 2002;100:1689-1698. doi:10.1182/blood-2002-01-0046. PMID:12176889
  • Dai G, Vaughn S, Zhang Y, Wang ET, Garcia-Cardena G, Gimbrone MA, Jr.. Biomechanical forces in atherosclerosis-resistant vascular regions regulate endothelial redox balance via phosphoinositol 3-kinase/Akt-dependent activation of Nrf2. Circ Res. 2007;101:723-733. doi:10.1161/CIRCRESAHA.107.152942
  • Zakkar M, Van der Heiden K, Luong lA, Chaudhury H, Cuhlmann S, Hamdulay SS, Krams R, Edirisinghe I, Rahman I, Carlsen H, et al. Activation of Nrf2 in endothelial cells protects arteries from exhibiting a proinflammatory state. Arterioscler Thromb Vasc Biol. 2009;29:1851-1857. doi:10.1161/ATVBAHA.109.193375. PMID:19729611
  • Fledderus JO, Boon RA, Volger OL, Hurttila H, Yla-Herttuala S, Pannekoek H, Levonen AL, Horrevoets AJ. KLF2 primes the antioxidant transcription factor Nrf2 for activation in endothelial cells. Arterioscler Thromb Vasc Biol. 2008;28:1339-1346. doi:10.1161/ATVBAHA.108.165811
  • Mohan S, Mohan N, Sprague EA. Differential activation of NF-kappa B in human aortic endothelial cells conditioned to specific flow environments. Am J Physiol. 1997;273:C572-C578. PMID:9277354
  • Nagel T, Resnick N, Dewey CF, Jr., Gimbrone MA, Jr.. Vascular endothelial cells respond to spatial gradients in fluid shear stress by enhanced activation of transcription factors. Arterioscler Thromb Vasc Biol. 1999;19:1825-1834. doi:10.1161/01.ATV.19.8.1825. PMID:10446060
  • Sabine A, Agalarov Y, Maby-El HH, Jaquet M, Hagerling R, Pollmann C, Bebber D, Pfenniger A, Miura N, Dormond O, et al. Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Dev Cell. 2012;22:430-445. doi:10.1016/j.devcel.2011.12.020
  • Nakajima H, Yamamoto K, Agarwala S, Terai K, Fukui H, Fukuhara S, Ando K, Miyazaki T, Yokota Y, Schmelzer E, et al. Flow-Dependent Endothelial YAP Regulation Contributes to Vessel Maintenance. Dev Cell. 2017;40:523-536. doi:10.1016/j.devcel.2017.02.019
  • Wang KC, Yeh YT, Nguyen P, Limqueco E, Lopez J, Thorossian S, Guan KL, Li YJ, Chien S. Flow-dependent YAP/TAZ activities regulate endothelial phenotypes and atherosclerosis. Proc Natl Acad Sci U S A. 2016;113:11525-11530. doi:10.1073/pnas.1613121113. PMID:27671657
  • Wang L, Luo JY, Li B, Tian XY, Chen LJ, Huang Y, Liu J, Deng D, Lau CW, Wan S, et al. Integrin-YAP/TAZ-JNK cascade mediates atheroprotective effect of unidirectional shear flow. Nature. 2016;540:579-582. doi:10.1038/nature20602.
  • Anderson KP, Kern CB, Crable SC, Lingrel JB. Isolation of a gene encoding a functional zinc finger protein homologous to erythroid Kruppel-like factor: Identification of a new multigene family. Mol Cell Biol. 1995;15:5957-5965. doi:10.1128/MCB.15.11.5957. PMID:7565748
  • Kuo CT, Veselits ML, Barton KP, Lu MM, Clendenin C, Leiden JM. The LKLF transcription factor is required for normal tunica media formation and blood vessel stabilization during murine embryogenesis. Genes Dev. 1997;11:2996-3006. doi:10.1101/gad.11.22.2996. PMID:9367982
  • Wang L, Zhang P, Wei Y, Gao Y, Patient R, Liu F. A blood flow-dependent klf2a-NO signaling cascade is required for stabilization of hematopoietic stem cell programming in zebrafish embryos. Blood. 2011;118:4102-4110. doi:10.1182/blood-2011-05-353235. PMID:21849483
  • Groenendijk BC, Hierck BP, Gittenberger-De Groot AC, Poelmann RE. Development-related changes in the expression of shear stress responsive genes KLF-2, ET-1, and NOS-3 in the developing cardiovascular system of chicken embryos. Dev Dyn. 2004;230:57-68. doi:10.1002/dvdy.20029. PMID:15108309
  • Lee JS, Yu Q, Shin JT, Sebzda E, Bertozzi C, Chen M, Mericko P, Stadtfeld M, Zhou D, Cheng L, et al. Klf2 is an essential regulator of vascular hemodynamic forces in vivo. Dev Cell. 2006;11:845-857. doi:10.1016/j.devcel.2006.09.006
  • Dekker RJ, van Thienen JV, Rohlena J, de Jager SC, Elderkamp YW, Seppen J, de Vries CJ, Biessen EA, van Berkel TJ, Pannekoek H, et al. Endothelial KLF2 links local arterial shear stress levels to the expression of vascular tone-regulating genes. Am J Pathol. 2005;167:609-618. doi:10.1016/S0002-9440(10)63002-7. PMID:16049344
  • Abe J, Berk BC. Novel mechanisms of endothelial mechanotransduction. Arterioscler Thromb Vasc Biol. 2014;34:2378-2386. doi:10.1161/ATVBAHA.114.303428. PMID:25301843
  • Doddaballapur A, Michalik KM, Manavski Y, Lucas T, Houtkooper RH, You X, Chen W, Zeiher AM, Potente M, Dimmeler S, et al. Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3. Arterioscler Thromb Vasc Biol. 2015;35:137-145. doi:10.1161/ATVBAHA.114.304277
  • Lin Z, Kumar A, SenBanerjee S, Staniszewski K, Parmar K, Vaughan DE, Gimbrone MA, Jr., Balasubramanian V, Garcia-Cardena G, Jain MK. Kruppel-like factor 2 (KLF2) regulates endothelial thrombotic function. Circ Res. 2005;96:e48-e57. doi:10.1161/01.RES.0000159707.05637.a1
  • Lin Z, Natesan V, Shi H, Dong F, Kawanami D, Mahabeleshwar GH, Atkins GB, Nayak L, Cui Y, Finigan JH, et al. Kruppel-like factor 2 regulates endothelial barrier function. Arterioscler Thromb Vasc Biol. 2010;30:1952-1959. doi:10.1161/ATVBAHA.110.211474
  • SenBanerjee S, Lin Z, Atkins GB, Greif DM, Rao RM, Kumar A, Feinberg MW, Chen Z, Simon DI, Luscinskas FW, et al. KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation. J Exp Med. 2004;199:1305-1315. doi:10.1084/jem.20031132. PMID:15136591
  • Atkins GB, Wang Y, Mahabeleshwar GH, Shi H, Gao H, Kawanami D, Natesan V, Lin Z, Simon DI, Jain MK. Hemizygous deficiency of Kruppel-like factor 2 augments experimental atherosclerosis. Circ Res. 2008;103:690-693. doi:10.1161/CIRCRESAHA.108.184663. PMID:18757824
  • Hamik A, Lin Z, Kumar A, Balcells M, Sinha S, Katz J, Feinberg MW, Gerzsten RE, Edelman ER, Jain MK. Kruppel-like factor 4 regulates endothelial inflammation. J Biol Chem. 2007;282:13769-13779. doi:10.1074/jbc.M700078200. PMID:17339326
  • Zhou G, Hamik A, Nayak L, Tian H, Shi H, Lu Y, Sharma N, Liao X, Hale A, Boerboom L, et al. Endothelial Kruppel-like factor 4 protects against atherothrombosis in mice. J Clin Invest. 2012;122:4727-4731. doi:10.1172/JCI66056. PMID:23160196
  • Nicoli S, Standley C, Walker P, Hurlstone A, Fogarty KE, Lawson ND. MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature. 2010;464:1196-1200. doi:10.1038/nature08889. PMID:20364122
  • Renz M, Otten C, Faurobert E, Rudolph F, Zhu Y, Boulday G, Duchene J, Mickoleit M, Dietrich AC, Ramspacher C, et al. Regulation of beta1 integrin-Klf2-mediated angiogenesis by CCM proteins. Dev Cell. 2015;32:181-190. doi:10.1016/j.devcel.2014.12.016
  • Kwon HB, Wang S, Helker CS, Rasouli SJ, Maischein HM, Offermanns S, Herzog W, Stainier DY. In vivo modulation of endothelial polarization by Apelin receptor signalling. Nat Commun. 2016;7:11805. doi:10.1038/ncomms11805
  • Wu J, Bohanan CS, Neumann JC, Lingrel JB. KLF2 transcription factor modulates blood vessel maturation through smooth muscle cell migration. J Biol Chem. 2008;283:3942-3950. doi:10.1074/jbc.M707882200. PMID:18063572
  • Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, et al. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol. 2012;14:249-256. doi:10.1038/ncb2441. PMID:22327366
  • Heckel E, Boselli F, Roth S, Krudewig A, Belting HG, Charvin G, Vermot J. Oscillatory Flow Modulates Mechanosensitive klf2a Expression through trpv4 and trpp2 during Heart Valve Development. Curr Biol. 2015;25:1354-1361. doi:10.1016/j.cub.2015.03.038
  • Vermot J, Forouhar AS, Liebling M, Wu D, Plummer D, Gharib M, Fraser SE. Reversing blood flows act through klf2a to ensure normal valvulogenesis in the developing heart. PLoS Biol. 2009;7:e1000246. doi:10.1371/journal.pbio.1000246. PMID:19924233
  • Steed E, Faggianelli N, Roth S, Ramspacher C, Concordet JP, Vermot J. klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis. Nat Commun. 2016;7:11646. doi:10.1038/ncomms11646. PMID:27221222
  • Hayden MS, Ghosh S. Shared principles in NF-kappaB signaling. Cell. 2008;132:344-362. doi:10.1016/j.cell.2008.01.020
  • Read MA, Whitley MZ, Williams AJ, Collins T. NF-kappa B and I kappa B alpha: An inducible regulatory system in endothelial activation. J Exp Med. 1994;179:503-512. doi:10.1084/jem.179.2.503. PMID:7507507
  • Karin M. The beginning of the end: IkappaB kinase (IKK) and NF-kappaB activation. J Biol Chem. 1999;274:27339-27342. doi:10.1074/jbc.274.39.27339. PMID:10488062
  • Wang C, Baker BM, Chen CS, Schwartz MA. Endothelial cell sensing of flow direction. Arterioscler Thromb Vasc Biol. 2013;33:2130-2136. doi:10.1161/ATVBAHA.113.301826. PMID:23814115
  • Feaver RE, Gelfand BD, Blackman BR. Human haemodynamic frequency harmonics regulate the inflammatory phenotype of vascular endothelial cells. Nat Commun. 2013;4:1525. doi:10.1038/ncomms2530. PMID:23443553
  • Bhullar IS, Li YS, Miao H, Zandi E, Kim M, Shyy JY, Chien S. Fluid shear stress activation of IkappaB kinase is integrin-dependent. J Biol Chem. 1998;273:30544-30549. doi:10.1074/jbc.273.46.30544. PMID:9804824
  • Collins T, Read MA, Neish AS, Whitley MZ, Thanos D, Maniatis T. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J. 1995;9:899-909. PMID:7542214
  • Khachigian LM, Resnick N, Gimbrone MA, Jr., Collins T. Nuclear factor-kappa B interacts functionally with the platelet-derived growth factor B-chain shear-stress response element in vascular endothelial cells exposed to fluid shear stress. J Clin Invest. 1995;96:1169-1175. doi:10.1172/JCI118106. PMID:7635955
  • Huo Y, Ley K. Adhesion molecules and atherogenesis. Acta Physiol Scand. 2001;173:35-43.doi:10.1046/j.1365-201X.2001.00882.x. PMID:11678724
  • Iiyama K, Hajra L, Iiyama M, Li H, DiChiara M, Medoff BD, Cybulsky MI. Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ Res. 1999;85:199-207. doi:10.1161/01.RES.85.2.199. PMID:10417402
  • Brand K, Page S, Rogler G, Bartsch A, Brandl R, Knuechel R, Page M, Kaltschmidt C, Baeuerle PA, Neumeier D. Activated transcription factor nuclear factor-kappa B is present in the atherosclerotic lesion. J Clin Invest. 1996;97:1715-1722. doi:10.1172/JCI118598. PMID:8601637
  • Cuhlmann S, Van der Heiden K, Saliba D, Tremoleda JL, Khalil M, Zakkar M, Chaudhury H, Luong lA, Mason JC, Udalova I, et al. Disturbed blood flow induces RelA expression via c-Jun N-terminal kinase 1: A novel mode of NF-kappaB regulation that promotes arterial inflammation. Circ Res. 2011;108:950-959. doi:10.1161/CIRCRESAHA.110.233841. PMID:21350211
  • Passerini AG, Polacek DC, Shi C, Francesco NM, Manduchi E, Grant GR, Pritchard WF, Powell S, Chang GY, Stoeckert CJ, Jr., et al. Coexisting proinflammatory and antioxidative endothelial transcription profiles in a disturbed flow region of the adult porcine aorta. Proc Natl Acad Sci U S A. 2004;101:2482-2487. doi:10.1073/pnas.0305938101. PMID:14983035
  • Orr AW, Sanders JM, Bevard M, Coleman E, Sarembock IJ, Schwartz MA. The subendothelial extracellular matrix modulates NF-kappaB activation by flow: A potential role in atherosclerosis. J Cell Biol. 2005;169:191-202. doi:10.1083/jcb.200410073. PMID:15809308
  • Shekhonin BV, Domogatsky SP, Idelson GL, Koteliansky VE, Rukosuev VS. Relative distribution of fibronectin and type I, III, IV, V collagens in normal and atherosclerotic intima of human arteries. Atherosclerosis. 1987;67:9-16. doi:10.1016/0021-9150(87)90259-0. PMID:3314885
  • Feaver RE, Gelfand BD, Wang C, Schwartz MA, Blackman BR. Atheroprone hemodynamics regulate fibronectin deposition to create positive feedback that sustains endothelial inflammation. Circ Res. 2010;106:1703-1711. doi:10.1161/CIRCRESAHA.109.216283
  • Jalali S, del Pozo MA, Chen K, Miao H, Li Y, Schwartz MA, Shyy JY, Chien S. Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands. Proc Natl Acad Sci U S A. 2001;98:1042-1046. doi:10.1073/pnas.031562998. PMID:11158591
  • Orr AW, Ginsberg MH, Shattil SJ, Deckmyn H, Schwartz MA. Matrix-specific suppression of integrin activation in shear stress signaling. Mol Biol Cell. 2006;17:4686-4697. doi:10.1091/mbc.E06-04-0289. PMID:16928957
  • Tzima E, del Pozo MA, Shattil SJ, Chien S, Schwartz MA. Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment. EMBO J. 2001;20:4639-4647. doi:10.1093/emboj/20.17.4639
  • Chen J, Green J, Yurdagul A, Jr., Albert P, McInnis MC, Orr AW. alphavbeta3 Integrins Mediate Flow-Induced NF-kappaB Activation, Proinflammatory Gene Expression, and Early Atherogenic Inflammation. Am J Pathol. 2015;185:2575-2589. doi:10.1016/j.ajpath.2015.05.013
  • Petzold T, Orr AW, Hahn C, Jhaveri KA, Parsons JT, Schwartz MA. Focal adhesion kinase modulates activation of NF-kappaB by flow in endothelial cells. Am J Physiol Cell Physiol. 2009;297:C814-C822. doi:10.1152/ajpcell.00226.2009. PMID:19587216
  • Sainson RC, Johnston DA, Chu HC, Holderfield MT, Nakatsu MN, Crampton SP, Davis J, Conn E, Hughes CC. TNF primes endothelial cells for angiogenic sprouting by inducing a tip cell phenotype. Blood. 2008;111:4997-5007. doi:10.1182/blood-2007-08-108597. PMID:18337563
  • Shono T, Ono M, Izumi H, Jimi SI, Matsushima K, Okamoto T, Kohno K, Kuwano M. Involvement of the transcription factor NF-kappaB in tubular morphogenesis of human microvascular endothelial cells by oxidative stress. Mol Cell Biol. 1996;16:4231-4239. doi:10.1128/MCB.16.8.4231. PMID:8754823
  • Yoshida A, Yoshida S, Ishibashi T, Kuwano M, Inomata H. Suppression of retinal neovascularization by the NF-kappaB inhibitor pyrrolidine dithiocarbamate in mice. Invest Ophthalmol Vis Sci. 1999;40:1624-1629. PMID:10359349
  • Santoro MM, Samuel T, Mitchell T, Reed JC, Stainier DY. Birc2 (cIap1) regulates endothelial cell integrity and blood vessel homeostasis. Nat Genet. 2007;39:1397-1402. doi:10.1038/ng.2007.8. PMID:17934460
  • Yu FX, Guan KL. The Hippo pathway: Regulators and regulations. Genes Dev. 2013;27:355-371. doi:10.1101/gad.210773.112
  • Piccolo S, Dupont S, Cordenonsi M. The biology of YAP/TAZ: Hippo signaling and beyond. Physiol Rev. 2014;94:1287-1312. doi:10.1152/physrev.00005.2014. PMID:25287865
  • Bertini E, Oka T, Sudol M, Strano S, Blandino: YAP: at the Crossroad Between Transformation and Tumor Suppression. Cell Cycle. 2009;8:49-57. doi:10.4161/cc.8.1.7259
  • Mauviel A, Nallet-Staub F, Varelas X. Integrating developmental signals: A Hippo in the (path)way. Oncogene. 2012;31:1743-1756. doi:10.1038/onc.2011.363. PMID:21874053
  • Harvey K, Tapon N: The Salvador-Warts-Hippo pathway – an emerging tumour-suppressor network. Nat Rev Cancer. 2007;7:182-191. doi:10.1038/nrc2070. PMID:17318211
  • Avruch J, Zhou D, Fitamant J, Bardeesy N, Mou F, Barrufet LR. Protein kinases of the Hippo pathway: Regulation and substrates. Semin Cell Dev Biol. 2012;23:770-784. doi:10.1016/j.semcdb.2012.07.002
  • Aragona M, Panciera T, Manfrin A, Giulitti S, Michielin F, Elvassore N, Dupont S, Piccolo S. A mechanical checkpoint controls multicellular growth through YAP/TAZ regulation by actin-processing factors. Cell. 2013;154:1047-1059. doi:10.1016/j.cell.2013.07.042
  • Calvo F, Ege N, Grande-Garcia A, Hooper S, Jenkins RP, Chaudhry SI, Harrington K, Williamson P, Moeendarbary E, Charras G, et al. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol. 2013;15:637-646. doi:10.1038/ncb2756. PMID:23708000
  • Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, Zanconato F, Le Diqabel J, Forcato M, Bicciato S, et al. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474:179-183. doi:10.1038/nature10137. PMID:21654799
  • Feng X, Degese MS, Iglesias-Bartolome R, Vaque JP, Molinolo AA, Rodrigues M, Zaidi MR, Ksander BR, Merlino G, Sodhi A, et al. Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry. Cancer Cell. 2014;25:831-845. doi:10.1016/j.ccr.2014.04.016
  • Benham-Pyle BW, Pruitt BL, Nelson WJ. Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and beta-catenin activation to drive cell cycle entry. Science 2015;348:1024-1027. doi:10.1126/science.aaa4559
  • Codelia VA, Sun G, Irvine KD. Regulation of YAP by mechanical strain through Jnk and Hippo signaling. Curr Biol. 2014;24:2012-2017. doi:10.1016/j.cub.2014.07.034
  • Cui Y, Hameed FM, Yang B, Lee K, Pan CQ, Park S, Sheetz M. Cyclic stretching of soft substrates induces spreading and growth. Nat Commun. 2015;6:6333. doi:10.1038/ncomms7333. PMID:25704457
  • Wada K, Itoga K, Okano T, Yonemura S, Sasaki H. Hippo pathway regulation by cell morphology and stress fibers. Development. 2011;138:3907-3914. doi:10.1242/dev.070987. PMID:21831922
  • Sabine A, Bovay E, Demir CS, Kimura W, Jaquet M, Agalarov Y, Zangger N, Scallan JP, Graber W, Gulpinar E, et al. FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature. J Clin Invest. 2015;125:3861-3877. doi:10.1172/JCI80454. PMID:26389677
  • Birukov KG, Birukova AA, Dudek SM, Verin AD, Crow MT, Zhan X, DePaola N, Garcia JG. Shear stress-mediated cytoskeletal remodeling and cortactin translocation in pulmonary endothelial cells. Am J Respir Cell Mol Biol. 2002;26:453-464. doi:10.1165/ajrcmb.26.4.4725
  • Chan SW, Lim CJ, Chong YF, Pobbati AV, Huang C, Hong W. Hippo pathway-independent restriction of TAZ and YAP by angiomotin. J Biol Chem. 2011;286:7018-7026. doi:10.1074/jbc.C110.212621. PMID:21224387
  • Mana-Capelli S, Paramasivam M, Dutta S, McCollum D. Angiomotins link F-actin architecture to Hippo pathway signaling. Mol Biol Cell. 2014;25:1676-1685. doi:10.1091/mbc.E13-11-0701. PMID:24648494
  • Zhao B, Tumaneng K, Guan KL. The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat Cell Biol. 2011;13:877-883. doi:10.1038/ncb2303. PMID:21808241
  • Fukui H, Terai K, Nakajima H, Chiba A, Fukuhara S, Mochizuki N. S1P-Yap1 signaling regulates endoderm formation required for cardiac precursor cell migration in zebrafish. Dev Cell. 2014;31:128-136. doi:10.1016/j.devcel.2014.08.014
  • Uemura M, Nagasawa A, Terai K. Yap/Taz transcriptional activity in endothelial cells promotes intramembranous ossification via the BMP pathway. Sci Rep. 2016;6:27473. doi:10.1038/srep27473. PMID:27273480
  • Oemar BS, Werner A, Garnier JM, Do DD, Godoy N, Nauck M, Marz W, Rupp J, Pech M, Luscher TF. Human connective tissue growth factor is expressed in advanced atherosclerotic lesions. Circulation. 1997;95:831-839. doi:10.1161/01.CIR.95.4.831. PMID:9054739
  • Cicha I, Yilmaz A, Klein M, Raithel D, Brigstock DR, Daniel WG, Goppelt-Struebe M, Garlichs CD. Connective tissue growth factor is overexpressed in complicated atherosclerotic plaques and induces mononuclear cell chemotaxis in vitro. Arterioscler Thromb Vasc Biol. 2005;25:1008-1013. doi:10.1161/01.ATV.0000162173.27682.7b
  • Chaqour B, Goppelt-Struebe M. Mechanical regulation of the Cyr61/CCN1 and CTGF/CCN2 proteins. FEBS J. 2006;273:3639-3649. doi:10.1111/j.1742-4658.2006.05360.x. PMID:16856934
  • Choi HJ, Zhang H, Park H, Choi KS, Lee HW, Agrawal V, Kim YM, Kwon YG. Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2. Nat Commun. 2015;6:6943. doi:10.1038/ncomms7943. PMID:25962877
  • Atkins GB, Simon DI. Interplay between NF-kappaB and Kruppel-like factors in vascular inflammation and atherosclerosis: location, location, location. J Am Heart Assoc. 2013;2:e000290. doi:10.1161/JAHA.113.000290
  • Kumar A, Lin Z, SenBanerjee S, Jain MK. Tumor necrosis factor alpha-mediated reduction of KLF2 is due to inhibition of MEF2 by NF-kappaB and histone deacetylases. Mol Cell Biol. 2005;25:5893-5903. doi:10.1128/MCB.25.14.5893-5903.2005
  • Xu Z, Yoshida T, Wu L, Maiti D, Cebotaru L, Duh EJ. Transcription factor MEF2C suppresses endothelial cell inflammation via regulation of NF-kappaB and KLF2. J Cell Physiol. 2015;230:1310-1320. doi:10.1002/jcp.24870. PMID:25474999
  • Fledderus JO, van Thienen JV, Boon RA, Dekker RJ, Rohlena J, Volger OL, Bijnens AP, Daemen MJ, Kuiper J, van Berkel TJ, et al. Prolonged shear stress and KLF2 suppress constitutive proinflammatory transcription through inhibition of ATF2. Blood. 2007;109:4249-4257. doi:10.1182/blood-2006-07-036020. PMID:17244683
  • Chu TJ, Peters DG. Serial analysis of the vascular endothelial transcriptome under static and shear stress conditions. Physiol Genomics. 2008;34:185-192. doi:10.1152/physiolgenomics.90201.2008. PMID:18505769
  • Kumar S, Kim CW, Son DJ, Ni CW, Jo H. Flow-dependent regulation of genome-wide mRNA and microRNA expression in endothelial cells in vivo. Sci Data. 2014;1:140039. doi:10.1038/sdata.2014.39. PMID:25977794
  • McCormick SM, Eskin SG, McIntire LV, Teng CL, Lu CM, Russell CG, Chittur KK. DNA microarray reveals changes in gene expression of shear stressed human umbilical vein endothelial cells. Proc Natl Acad Sci U S A. 2001;98:8955-8960. doi:10.1073/pnas.171259298. PMID:11481467
  • Ohura N, Yamamoto K, Ichioka S, Sokabe T, Nakatsuka H, Baba A, Shibata M, Nakatsuka T, Harii K, Wada Y, et al. Global analysis of shear stress-responsive genes in vascular endothelial cells. J Atheroscler Thromb. 2003;10:304-313. doi:10.5551/jat.10.304. PMID:14718748
  • Ni CW, Qiu H, Rezvan A, Kwon K, Nam D, Son DJ, Visvader JE, Jo H. Discovery of novel mechanosensitive genes in vivo using mouse carotid artery endothelium exposed to disturbed flow. Blood. 2010;116:e66-e73. doi:10.1182/blood-2010-04-278192. PMID:20551377
  • Son DJ, Kumar S, Takabe W, Kim CW, Ni CW, Alberts-Grill N, Jang IH, Kim S, Kim W, Won KS, et al. The atypical mechanosensitive microRNA-712 derived from pre-ribosomal RNA induces endothelial inflammation and atherosclerosis. Nat Commun. 2013;4:3000. doi:10.1038/ncomms4000. PMID:24346612
  • Espin-Palazon R, Stachura DL, Campbell CA, Garcia-Moreno D, Del Cid N, Kim AD, Candel S, Meseguer J, Mulero V, Traver D. Proinflammatory signaling regulates hematopoietic stem cell emergence. Cell. 2014;159:1070-1085. doi:10.1016/j.cell.2014.10.031
  • He Q, Zhang C, Wang L, Zhang P, Ma D, Lv J, Liu F. Inflammatory signaling regulates hematopoietic stem and progenitor cell emergence in vertebrates. Blood. 2015;125:1098-1106. doi:10.1182/blood-2014-09-601542. PMID:25540193

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