{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T04:27:17Z","timestamp":1791606437354,"version":"4.3.4"},"reference-count":54,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:p>Transgenic overexpression of calcineurin (CN\/Tg) in mouse cardiac myocytes results in hypertrophy followed by dilation, dysfunction, and sudden death. Nitric oxide (NO) produced via inducible NO synthase (iNOS) has been implicated in cardiac injury. Since calcineurin regulates iNOS expression, and since phenotypes of mice overexpressing iNOS are similar to CN\/Tg, we hypothesized that iNOS is pathogenically involved in cardiac phenotypes of CN\/Tg mice. CN\/Tg mice had increased serum and cardiac iNOS levels. When CN\/Tg-iNOS<jats:sup>\u2212\/\u2212<\/jats:sup>and CN\/Tg mice were compared, some phenotypes were similar: extent of hypertrophy and fibrosis. However, CN\/Tg-iNOS<jats:sup>\u2212\/\u2212<\/jats:sup>mice had improved systolic performance ( P &lt; 0.001) and less heart block ( P &lt; 0.0001); larger sodium current density and lower serum TNF-\u03b1 levels ( P &lt; 0.03); and less apoptosis ( P &lt; 0.01) resulting in improved survival ( P &lt; 0.0003). To define tissue origins of iNOS production, chimeric lines were generated. Bone marrow (BM) from wild-type or iNOS<jats:sup>\u2212\/\u2212<\/jats:sup>mice was transplanted into CN\/Tg mice. iNOS deficiency restricted to BM-derived cells was not protective. Calcineurin activates the local production of NO by iNOS in cardiac myocytes, which significantly contributes to sudden death, heart block, left ventricular dilation, and impaired systolic performance in this murine model of cardiac hypertrophy induced by the overexpression of calcineurin.<\/jats:p>","DOI":"10.1152\/ajpheart.00386.2008","type":"journal-article","created":{"date-parts":[[2008,7,12]],"date-time":"2008-07-12T01:06:50Z","timestamp":1215824810000},"page":"H1122-H1131","source":"Crossref","is-referenced-by-count":15,"title":["iNOS in cardiac myocytes plays a critical role in death in a murine model of hypertrophy induced by calcineurin"],"prefix":"10.1152","volume":"295","author":[{"given":"Julie R.","family":"Somers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Lees-Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Roach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Loken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Semeniuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry J.","family":"Duff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1161\/hh2301.100801"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.10.1846"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1042\/CS20050087"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043399"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.01.032"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000107197.99679.77"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2005.12.008"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00230-4"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0419com"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.18.13571"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.3.255"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-005-2447-0"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00661-2"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01122.2006"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00872.2001"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00535.x"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01247.2005"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(02)01947-7"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.07.007"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.10.937"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2003.12.153"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2001.1393"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1007\/s004240050870"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-5717fje"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2004.11.029"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.20.2431"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100452200"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1161\/hy02t2.102796"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10368"},{"key":"R30","doi-asserted-by":"crossref","unstructured":"Mitsuyama H, Kambe F, Murakami R, Cao X, Ishiguro N, Seo H.Calcium signaling pathway involving calcineurin regulates interleukin-8 gene expression through activation of NF-kappaB in human osteoblast-like cells.J Bone Miner Res19: 671\u2013679, 2004.","DOI":"10.1359\/JBMR.0301256"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1161\/hh1201.093159"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.9.731"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81573-1"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0213265"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020762401408"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.05.026"},{"key":"R37","doi-asserted-by":"crossref","unstructured":"Oum JH, Han J, Myung H, Hleb M, Sharma S, Park J.Molecular mechanism of NFAT family proteins for differential regulation of the IL-2 and TNF-alpha promoters.Mol Cell13: 77\u201384, 2002.","DOI":"10.1016\/S1016-8478(23)15006-0"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.04.030"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(03)00546-7"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00546.2002"},{"key":"R41","unstructured":"Shimojo N, Jesmin S, Zaedi S, Soma M, Kobayashi T, Maeda S, Yamaguchi I, Goto K, Miyauchi T.EPA effect on NOS gene expression and on NO level in endothelin-1-induced hypertrophied cardiomyocytes.Exp Biol Med (Maywood)231: 913\u2013918, 2006."},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(96)88617-2"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00395-8"},{"key":"R44","unstructured":"Tan JX, Liu CZ, Jie YL, Wang Y, Huang YG.Effect of cyclosporine A on myocardial calcineurin activity of the right ventricle and plasma NO, nitric oxide synthase and endothelin-1 levels in rats with chronic hypoxia.Di Yi Jun Yi Da Xue Xue Bao24: 656\u2013658, 2004."},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)01130-5"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.16.6084-6094.2000"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.5.2337"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.07.121"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2000.1296"},{"key":"R50","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.086686"},{"key":"R51","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.21.6.3720"},{"key":"R52","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000264081.78659.45"},{"key":"R53","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.089672"},{"key":"R54","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20802"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00386.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T07:36:01Z","timestamp":1709105761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00386.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,9]]},"references-count":54,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2008,9]]}},"alternative-id":["10.1152\/ajpheart.00386.2008"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00386.2008","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,9]]}}}