{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:47:31Z","timestamp":1791096451055,"version":"4.1.0"},"reference-count":128,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,3,27]],"date-time":"2003-03-27T00:00:00Z","timestamp":1048723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2003,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heme oxygenase\u20101 (HO\u20101) catalyzes the degradation of heme to carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently metabolized to bilirubin by the enzyme biliverdin reductase. Although interest in HO\u20101 originally centered on its heme\u2010degrading function, recent findings indicate that HO\u20101 exerts other biologically important actions. Emerging evidence suggests that HO\u20101 plays a critical role in growth regulation. Deletion of the <jats:italic>HO\u20101<\/jats:italic> gene or inhibition of HO\u20101 activity results in growth retardation and impaired fetal development, whereas HO\u20101 overexpression increases body size. Although the mechanisms responsible for the growth promoting properties of HO\u20101 are not well established, HO\u20101 can indirectly influence growth by regulating the synthesis of growth factors and by modulating the delivery of oxygen or nutrients to specific target tissues. In addition, HO\u20101 exerts important effects on critical determinants of tissue size, including cell proliferation, apoptosis, and hypertrophy. However, the actions of HO\u20101 are highly variable and may reflect a role for HO\u20101 in maintaining tissue homeostasis. Considerable evidence supports a crucial role for HO\u20101 in blocking the growth of vascular smooth muscle cells (SMCs). This antiproliferative effect of HO\u20101 is mediated primarily via the release of CO, which inhibits vascular SMC growth via multiple pathways. Pharmacologic or genetic approaches targeting HO\u20101 or CO to the blood vessel wall may represent a promising, novel therapeutic approach in treating vascular proliferative disorders. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.10274","type":"journal-article","created":{"date-parts":[[2003,4,16]],"date-time":"2003-04-16T10:45:16Z","timestamp":1050489916000},"page":"373-382","source":"Crossref","is-referenced-by-count":132,"title":["Heme oxygenase\u20101 in growth control and its clinical application to vascular disease"],"prefix":"10.1002","volume":"195","author":[{"given":"William","family":"Durante","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2003,3,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.15.6798"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1995.414"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/beog.2000.0139"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401783"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1020"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.059002645.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7903"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2002.0845"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.00-0376com"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0702261"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0966-3274(02)00037-0"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.1.82"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.7.1015"},{"key":"e_1_2_9_15_1","first-page":"497","article-title":"Inhibition of platelet aggregation by carbon monoxide is mediated by the activation of soluble guanylate cyclase","volume":"32","author":"Brune B","year":"1987","journal-title":"Mol Pharmacol"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1990.tb19276.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0769-4"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(97)00667-9"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.91.9.2306"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7742"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.2.H643"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200207150-00017"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02594-4"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(19980101)68:1<121::AID-JCB12>3.0.CO;2-K"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6690624"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2445"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/89068"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1089\/152308602753666280"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1191\/1358863x02vm424ra"},{"key":"e_1_2_9_30_1","first-page":"45","volume-title":"Carbon monoxide and cardiovascular functions","author":"Durante W","year":"2002"},{"key":"e_1_2_9_31_1","first-page":"255","article-title":"Carbon monoxide and vascular cell function (a review)","volume":"2","author":"Durante W","year":"1998","journal-title":"Int J Mol Med"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/152660280100800501"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/11072"},{"key":"e_1_2_9_34_1","first-page":"357","article-title":"Adeno\u2010associated virus vectors for gene therapy","volume":"2","author":"Flotte TR","year":"1995","journal-title":"Gene Ther"},{"key":"e_1_2_9_35_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1124\/mol.53.1.123","article-title":"Mechanism of YC\u20101\u2010induced activation of soluble guanylate cyclase","volume":"53","author":"Friebe A","year":"1998","journal-title":"Mol Pharmacol"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01078.x"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/87929"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-214-44069"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/3982"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3973"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3530459"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1089\/104454902753759726"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00443-3"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00046.x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.88.5.506"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.25.2.166"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc3801.095663"},{"key":"e_1_2_9_48_1","first-page":"22:1680","article-title":"Heme oxygenase\u20101 gene promoter polymorphism is associated with coronary artery disease in Japanese patients with coronary risk factors","author":"Kaneda H","year":"2002","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1258"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1089\/104303402320138970"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.1.99"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000017167.26718.F2"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(91)90478-I"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.19.10393"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1999.tb00091.x"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114686"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02054-5"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0741-3_39"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00410-8"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc0102.101369"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(94)90067-1"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.14.1.208"},{"key":"e_1_2_9_63_1","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1096\/fasebj.2.10.3290025","article-title":"Heme oxygenase: Function, multiplicity, regulatory mechanisms, and clinical applications","volume":"2","author":"Maines MD","year":"1989","journal-title":"FASEB J"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(96)00010-6"},{"key":"e_1_2_9_65_1","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/S0021-9258(17)42488-4","article-title":"Characterization of two constitutive forms of liver microsomal heme oxygenase","volume":"261","author":"Maines MD","year":"1986","journal-title":"J Biol Chem"},{"key":"e_1_2_9_66_1","first-page":"433","article-title":"Significance of heme oxygenase in prolactin\u2010mediated cell proliferation and angiogenesis in human endothelial cells","volume":"10","author":"Malaguarnera L","year":"2002","journal-title":"Int J Mol Med"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.00725.x"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1053\/plac.2000.0574"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc0502.103363"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.161272598"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118334"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.5.1475"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.52.32804"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh0202.104530"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.1.317"},{"key":"e_1_2_9_76_1","first-page":"1107","article-title":"Macrophage infiltration and heme oxygenase\u20101 expression correlate with angiogenesis in human gliomas","volume":"5","author":"Nishie A","year":"1999","journal-title":"Clin Cancer Res"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.6.1414"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5342"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/74680"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0213190"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1999.721187.x"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00230871"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.2000.278.2.L312"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.12.4443"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.9.1983"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.20.10919"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.20.10925"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(89)90347-X"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198602203140806"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.38.2.210"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.6.4185"},{"key":"e_1_2_9_92_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1177\/152660280200900401","article-title":"Heme oxygenase\u20101 genotype is a vascular anti\u2010inflammatory factor following balloon angioplasty","volume":"9","author":"Schillinger M","year":"2002","journal-title":"J Endovasc Ther"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0049-3848(02)00100-7"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.58.4.427"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(99)00338-0"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.278.5.F726"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00015-0"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(98)00278-8"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1038\/2063"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.4851"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715769009148577"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3029864"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00184a036"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.13.1800"},{"key":"e_1_2_9_105_1","first-page":"6388","article-title":"The enzymatic conversion of heme to bilirubin by microsomal heme oxgyenase","volume":"244","author":"Tenhunen R","year":"1968","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)63477-5"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00568.x"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.3.1305"},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.2.H623"},{"key":"e_1_2_9_110_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2000.tb01033.x"},{"key":"e_1_2_9_111_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3835(98)00372-3"},{"key":"e_1_2_9_112_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3942"},{"key":"e_1_2_9_113_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc4701.099585"},{"key":"e_1_2_9_114_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(00)00552-9"},{"key":"e_1_2_9_115_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2002.6552"},{"key":"e_1_2_9_116_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00326-X"},{"key":"e_1_2_9_117_1","doi-asserted-by":"crossref","first-page":"14678","DOI":"10.1016\/S0021-9258(18)82386-9","article-title":"Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to heme oxygenase\u2010dependent increase in ferritin","volume":"268","author":"Vile GF","year":"1993","journal-title":"J Biol Chem"},{"key":"e_1_2_9_118_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00133.2002"},{"key":"e_1_2_9_119_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119569"},{"key":"e_1_2_9_120_1","doi-asserted-by":"publisher","DOI":"10.1139\/y97-187"},{"key":"e_1_2_9_121_1","first-page":"637","article-title":"Expression of endogenous heme oxygenase on surface of placental trophoblasts of pregnant women with intrauterine growth retardation of the fetus","volume":"22","author":"Wang YP","year":"2002","journal-title":"Di Yi Jun Yi Da Xue Xue Bao"},{"key":"e_1_2_9_122_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0196-87"},{"key":"e_1_2_9_123_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI4165"},{"key":"e_1_2_9_124_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6163"},{"key":"e_1_2_9_125_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh1401.093314"},{"key":"e_1_2_9_126_1","doi-asserted-by":"crossref","first-page":"7778","DOI":"10.1016\/S0021-9258(18)34449-1","article-title":"Purification and properties of bovine spleen heme oxygenase: Amino acid composition and sites of action of inhibitors of heme oxygenase","volume":"257","author":"Yoshinaga T","year":"1992","journal-title":"J Biol Chem"},{"key":"e_1_2_9_127_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(01)02071-4"},{"key":"e_1_2_9_128_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290118"},{"key":"e_1_2_9_129_1","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1982.01380350016003"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.10274","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.10274","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,9]],"date-time":"2023-10-09T13:17:53Z","timestamp":1696857473000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.10274"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3,27]]},"references-count":128,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2003,6]]}},"alternative-id":["10.1002\/jcp.10274"],"URL":"https:\/\/doi.org\/10.1002\/jcp.10274","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,3,27]]}}}