{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:05:28Z","timestamp":1773662728165,"version":"3.50.1"},"reference-count":55,"publisher":"Japanese Circulation Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Jpn Circ J"],"published-print":{"date-parts":[[2001]]},"DOI":"10.1253\/jcj.65.353","type":"journal-article","created":{"date-parts":[[2002,9,11]],"date-time":"2002-09-11T02:17:28Z","timestamp":1031710648000},"page":"353-358","source":"Crossref","is-referenced-by-count":37,"title":["Molecular Mechanism of Cardiac Hypertrophy and Development"],"prefix":"10.1253","volume":"65","author":[{"given":"Issei","family":"Komuro","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"330","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Levy D, Garrison RJ, Savage DD, Kannel WB, Castelli WP: Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study. N Engl J Med 1990; 322: 1561-1566","DOI":"10.1056\/NEJM199005313222203"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Baker KM, Booz GW, Dostal DE: Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system. Annu Rev Physiol 1992; 54: 227-241","DOI":"10.1146\/annurev.ph.54.030192.001303"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Mann DL, Kent RL, Cooper G: Load regulation of the properties of adult feline cardiocytes: Growth induction by cellular deformation. Circ Res 1989; 64: 1079-1090","DOI":"10.1161\/01.RES.64.6.1079"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Komuro I, Kaida T, Shibazaki Y, Kurabayashi M, Katoh Y, Hoh E, et al: Streching cardiac myocytes stimulates protooncogene expression. J Biol Chem 1990; 265: 3595-3598","DOI":"10.1016\/S0021-9258(19)39631-0"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Komuro I, Katoh Y, Kaida T, Shibazaki Y, Kurabayashi M, Takaku F, et al: Mechanical loading stimulates cell hypertrophy and specific gene expression in cultured rat cardiac myocytes: Possible role of protein kinase C activation. J Biol Chem 1991; 266: 1265-1268","DOI":"10.1016\/S0021-9258(17)35310-3"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Komuro I, Yazaki Y: Control of cardiac gene expression by mechanical stress. Annu Rev Physiol 1993; 55: 55-75","DOI":"10.1146\/annurev.ph.55.030193.000415"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Sadoshima J, Izumo S: The cellular and molecular response of cardiac myocytes to mechanical stress. Annu Rev Physiol 1997; 59: 551-571","DOI":"10.1146\/annurev.physiol.59.1.551"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Hammond GL, Wieben E, Market CL: Molecular signals for initiating protein synthesis in organ hypertrophy. Proc Natl Acad Sci USA 1979; 76: 2455-2459","DOI":"10.1073\/pnas.76.5.2455"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Schnkert H, Dzau VJ, Tang SS, Hirsch AT, Apstein CS, Lorell BH: Increased rat cardiac angiotensin converting enzyme activity and mRNA expression, in pressure overload left ventricular hypertrophy: Effects on coronary resistance, contractility, and relaxation. J Clin Invest 1990; 86: 1913-1920","DOI":"10.1172\/JCI114924"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Linz W, Schoelkens BA, Ganten D: Converting enzyme inhibition specifically prevents the development and induces regression of cardiac hypertrophy in rats. Clin Exp Hypertens 1989; 11: 1325-1350","DOI":"10.3109\/10641968909038172"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Baker KM, Cherin MI, Wixon SK, Aceto JF: Renin-angiotensin system involvement in presure-overload cardiac hypertrophy in rats. Am J Physiol 1990; 259: H324-H332","DOI":"10.1152\/ajpheart.1990.259.2.H324"},{"key":"12","doi-asserted-by":"crossref","first-page":"II-450","DOI":"10.1161\/01.CIR.80.3.450","volume":"80","year":"1989","unstructured":"12. Katoh Y, Komuro I, Shibasaki Y, Yamaguchi H, Yazaki Y: Angiotensin II induces hypertrophy and oncogene expression in cultured rat heart myocytes (abstract). Circulation 1989; 80: II-450","journal-title":"Circulation","ISSN":"https:\/\/id.crossref.org\/issn\/0009-7322","issn-type":"print"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Sadoshima J, Izumo S: Molecular characterization of angiotenshin II induce hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts: Critical role of the AT1 receptor subtype. Circ Res 1993; 73: 413-423","DOI":"10.1161\/01.RES.73.3.413"},{"key":"14","doi-asserted-by":"publisher","unstructured":"14. Sadoshima J, Xu Y, Slayter HS, Izumo S: Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 1993; 75: 977-984","DOI":"10.1016\/0092-8674(93)90541-W"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Yamazaki T, Komuro I, Kudoh S, Zou Y, Shiojima I, Mizuno T, et al: Angiotenshin II partly mediates mechanical stress induced cardiac hypertrophy. Circ Res 1995; 77: 258-265","DOI":"10.1161\/01.RES.77.2.258"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Sadoshima J, Izumo S: The heterotrimeric Gq protein-coupled antiotensin II receptor activates p21 ras via the tyrosine kinase-Shc-Grb2-Sos pathway in cardiac myocytes. EMBO J 1996; 15: 775-787","DOI":"10.1002\/j.1460-2075.1996.tb00413.x"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Zou Y, Komuro I, Yamazaki T, Kudoh S, Aikawa R, Uozumi H, et al: Cell type-specific angiotensin II-evoked signal transduction pathways: Critical roles of G subunit, Src family, and Ras in cardiac fibroblasts. Circ Res 1998; 82: 337-345","DOI":"10.1161\/01.RES.82.3.337"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Zou Y, Komuro I, Yamazaki T, Aikawa R, Kudoh S, Shiojima I, et al: Protein kinase C, but not tyrosine kinases or Ras, plays a critical role in angiotensin II-induced activation of Raf-1Kinase and extracellular signal-regulated protein kinases in cardiac myocytes. J Biol Chem 1996; 271: 33592-33597","DOI":"10.1074\/jbc.271.52.33592"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Ito H, Hirata Y, Adachi S, Tanaka M, Tsujino M, Koike A, et al: Endothelin-1 is an autocrine\/paracrine factor in the mechanism of angiotensin II-induced hypertrophy in cultured rat cardiomyocytes. J Clin Invest 1993; 92: 398-403","DOI":"10.1172\/JCI116579"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Yamazaki T, Komuro I, Kudoh S, Zou Y, Shiojima I, Hiroi Y, et al: Endothelin-1 is involved in mechanical stress-induced cardiomyocyte hypertrophy. J Biol Chem 1996; 271: 3221-3228","DOI":"10.1074\/jbc.271.6.3221"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Harada M, Itoh H, Nakagawa O, Ogawa Y, Miyamoto Y, Kuwahara K, et al: Significance of ventricular myocytes and nonmyocytes interaction during cardiocyte hypertrophy: Evidence for endothelin-1 as a paracrine hypertrophic factor from cardiac nonmyocytes. Circulation 1997; 96: 3737-3744","DOI":"10.1161\/01.CIR.96.10.3737"},{"key":"22","doi-asserted-by":"publisher","unstructured":"22. Sakai S, Miyauchi T, Kobayashi M, Yamaguchi I, Goto K, Sugishita Y: Inhibition of myocardial endothelin pathway improves long-term survival heart failure. Nature 1996; 384: 353-355","DOI":"10.1038\/384353a0"},{"key":"23","doi-asserted-by":"publisher","unstructured":"23. Akhter SA, Luttrell LM, Rockman HA, Iaccarino G, Lefkowitz RJ, Koch WJ: Targeting the receptor-G interface to inhibit vivo pressure overload myocardial hypertrophy. Science 1998; 280: 574-577","DOI":"10.1126\/science.280.5363.574"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Morris CE: Mechanosensitive ion channels. J Membr Biol 1990; 113: 93-107","DOI":"10.1007\/BF01872883"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Bustamante JO, Ruknudin A, Sachs F: Stretch-activated channels in heart cells: Relevance to cardiac hypertrophy. J Cardiovasc Pharmacol 1991; 17: S110-S117","DOI":"10.1097\/00005344-199117002-00024"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Sigurdson W, Ruknudin A, Sachs F: Calcium imaging of mechanically induced fluxes in tissue-cultured chick heart: Role of stretch-activated ion channels. Am J Physiol 1992; 262: H1110-H1115","DOI":"10.1152\/ajpheart.1992.262.4.H1110"},{"key":"27","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0092-8674(00)81573-1","volume":"93","year":"1998","unstructured":"27. Molkentin JD, Lu J-R, Antos CL, Markham B, Richardson J, Robbins J, et al: A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell 1998; 93: 215-228","journal-title":"Cell","ISSN":"https:\/\/id.crossref.org\/issn\/0092-8674","issn-type":"print"},{"key":"28","doi-asserted-by":"publisher","unstructured":"28. Shimoyama M, Hayashi D, Takimoto E, Zou Y, Oka T, Uozumi H, et al: Calcineurin plays a critical role, in pressure overload-induced cardiac hypertrophy. Circulation 1999; 100: 2449-2454","DOI":"10.1161\/01.CIR.100.24.2449"},{"key":"29","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1161\/01.CIR.102.16.1996","volume":"102","year":"2000","unstructured":"29. Shimoyama M, Hayashi D, Zou Y, Takimoto E, Mizukami M, Monzen K, et al: Calcineurin inhibitor attenuates the development and induces the regression of cardiac hypertrophy in rats with salt-sensitive hypertension. Circulation 2000; 102: 1996-2004","journal-title":"Circulation","ISSN":"https:\/\/id.crossref.org\/issn\/0009-7322","issn-type":"print"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. Juliano RL, Haskill S: Signal transduction from the extracellular matrix. J Cell Biol 1993; 120: 577-585","DOI":"10.1083\/jcb.120.3.577"},{"key":"31","doi-asserted-by":"publisher","unstructured":"31. Hynes RO: Integrins: Versatility, modulation, and signaling in cell. Cell 1992; 69: 11-25","DOI":"10.1016\/0092-8674(92)90115-S"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32. Hamasaki K, Mimura T, Furuya H, Morino N, Yamazaki T, Komuro I, et al: Streching mesangial cells stimulates tyrosine phosphorylation of focal adhesion kinase pp125FAK. Biochem Biophys Res Commun 1995; 212: 544-549","DOI":"10.1006\/bbrc.1995.2004"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33. Mackay DJ, Hall A: Rho GTPases. J Biol Chem 1998; 273: 20685-20688","DOI":"10.1074\/jbc.273.33.20685"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34. Aikawa R, Komuro I, Yamazaki T, Kudoh S, Zou Y, Zhu W, et al: Angiotensin II activates RhoA in cardiac myocytes: A critical role of RhoA in angiotensin II-induced premyofibril formation. Circ Res 1998; 82: 666-676","DOI":"10.1161\/01.RES.82.6.666"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Thorburn J, Xu S, Thorburn A: MAP kinase- and Rho-dependent signals interact to regulate gene expression but not actin morphology in cardiac muscle cells. EMBO J 1997; 16: 1888-1900","DOI":"10.1093\/emboj\/16.8.1888"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36. Sah VP, Hoshijima M, Chien KR, Brown JH: Rho is required for G and adrenergic receptor signalling in cardiomyocytes. J Biol Chem 1996; 271: 31185-31190","DOI":"10.1074\/jbc.271.49.31185"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37. Aoki H, Izumo S, Sadoshima J: Angiotensin II activates RhoA in cardiac myocytes: A critical role of RhoA in angiotensin II-induced premyofibril formation. Circ Res 1998; 82: 666-676","DOI":"10.1161\/01.RES.82.6.666"},{"key":"38","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1126\/science.7681220","volume":"259","year":"1993","unstructured":"38. Brewster JL, de Valoir T, Dwyer ND, Winter E, Gustin MC: An osmosensing signal transduction pathway in yeast. Science 1993; 259: 1760-1763","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39. Komuro I, Izumo S: Csx: A murine homeobox-containing gene specifically expressed in the developing heart. Proc Natl Acad Sci USA 1993; 90: 8145-8149","DOI":"10.1073\/pnas.90.17.8145"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40. Lints TJ, Parsons LM, Hartley L, Lyons I, Harvey RP: Nkx-2.5: A novel murine homeobox gene expressed in early heart progenitor cells and their myogeni descendants. Development 1993; 119: 419-431","DOI":"10.1242\/dev.119.2.419"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41. Azpiazu N, Frasch M: Tinman and bagpipe: Two homeobox genes that determine cell fates in the dorsal mesoderm of Drosophila. Genes Dev 1993; 7: 1325-1340","DOI":"10.1101\/gad.7.7b.1325"},{"key":"42","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1242\/dev.118.3.719","volume":"118","year":"1993","unstructured":"42. Bodmer R: The gene tinman is required for specification of the heart and visceral muscles in Drosophila. Development 1993; 118: 719-729","journal-title":"Development","ISSN":"https:\/\/id.crossref.org\/issn\/0950-1991","issn-type":"print"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43. Lyons I, Parsons LM, Hartley L, Li R, Andrews JE, Robb L, et al: Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeobox gene Nkx2-5. Genes Dev 1995; 9: 1654-1666","DOI":"10.1101\/gad.9.13.1654"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44. Tonissen KF, Drysdale TA, Lints TJ, Harvey RP, Krieg PA: XNkx-2.5, a <i>Xenopus<\/i> gene related to Nkx-2.5 and tinman: Evidence for a conserved role in cardiac development. Dev Biol 1994; 162: 325-328","DOI":"10.1006\/dbio.1994.1089"},{"key":"45","doi-asserted-by":"crossref","first-page":"4203","DOI":"10.1242\/dev.121.12.4203","volume":"121","year":"1995","unstructured":"45. Schultheiss TM, Xydas S, Lassar AB: Induction of avian cardiac myogenesis by anterior endoderm. Development 1995; 121: 4203-4214","journal-title":"Development","ISSN":"https:\/\/id.crossref.org\/issn\/0950-1991","issn-type":"print"},{"key":"46","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1242\/dev.122.12.3809","volume":"122","year":"1996","unstructured":"46. Chen JN, Fishman MC: Zebrafish tinman homeolog demarcates the heart and initiates myocardial differentiation. Development 1996; 122: 3809-3816","journal-title":"Development","ISSN":"https:\/\/id.crossref.org\/issn\/0950-1991","issn-type":"print"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47. Shiojima I, Komuro I, Mizuno T, Aikawa R, Akazawa H, Oka T, et al: Molecular cloning and characterization of human cardiac homeobox gene CSX1. Circ Res 1996; 79: 920-929","DOI":"10.1161\/01.RES.79.5.920"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48. Bodmer R: Heart development in <i>Drosophila<\/i> and its relationship to vertebrates. Trends Cardiovasc Med 1995; 5: 21-28","DOI":"10.1016\/1050-1738(94)00032-Q"},{"key":"49","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1126\/science.272.5262.671","volume":"272","year":"1996","unstructured":"49. Olson EN, Srivastava D: Molecular pathway controlling heart development. Science 1996; 272: 671-676","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"key":"50","doi-asserted-by":"crossref","unstructured":"50. Harvey RP: NK-2 homeobox genes and heart development. Dev Biol 1996; 178: 203-216","DOI":"10.1006\/dbio.1996.0212"},{"key":"51","doi-asserted-by":"crossref","unstructured":"51. Shiojima I, Komuro I, Oka T, Hiroi Y, Mizuno T, Takimoto E, et al: Context-dependent transcriptional cooperation mediated by cardiac transcription factors Csx\/Nkx-2.5 and GATA-4. J Biol Chem 1999; 274: 8231-8239","DOI":"10.1074\/jbc.274.12.8231"},{"key":"52","doi-asserted-by":"publisher","unstructured":"52. Frasch M: Induction of visceral and cardiac mesoderm by ectodermal Dpp in the early <i>Drosophila<\/i> embryo. Nature 1995; 374: 464-467","DOI":"10.1038\/374464a0"},{"key":"53","doi-asserted-by":"crossref","unstructured":"53. Monzen K, Shiojima I, Hiroi Y, Kudoh S, Oka T, Takimoto E, et al: Bone morphogenetic protein induces cardiomyocyte differentiation through the mitogen-activated protein kinase kinase kinase TAK1 and cardiac transcription factors Csx\/Nkx2.5 and GATA-4. Mol Cell Biol 1999; 19: 7096-7105","DOI":"10.1128\/MCB.19.10.7096"},{"key":"54","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1126\/science.270.5244.2008","volume":"270","year":"1995","unstructured":"54. Yamaguchi K, Shirakabe K, Shibuya H, Irie K, Oishi N, Ueno T, et al: Indentification of a member of the MAPKKK family as a potential mediator of TGF-&alpha; signal transduction. Science 1995; 270: 2008-2011","journal-title":"Science","ISSN":"https:\/\/id.crossref.org\/issn\/0036-8075","issn-type":"print"},{"key":"55","doi-asserted-by":"crossref","unstructured":"55. Schultheiss TM, Burch JBE, Lassar AB: A role for bone morphogenetic proteins in the induction of cardiac myogenesis. Genes Dev 1997; 11: 451-462","DOI":"10.1101\/gad.11.4.451"}],"container-title":["Japanese Circulation Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jcj\/65\/5\/65_5_353\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T21:19:59Z","timestamp":1622150399000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jcj\/65\/5\/65_5_353\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001]]},"references-count":55,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2001]]}},"URL":"https:\/\/doi.org\/10.1253\/jcj.65.353","relation":{},"ISSN":["0047-1828","1347-4839"],"issn-type":[{"value":"0047-1828","type":"print"},{"value":"1347-4839","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001]]}}}