{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T21:01:33Z","timestamp":1787950893153,"version":"build-2784847793"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,3,24]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>S-nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in the pathogenesis of cardiovascular disease. The aim of this study was to determine the role of SNO of MLP (muscle LIM protein) in myocardial hypertrophy, as well as the mechanism by which SNO-MLP modulates hypertrophic growth in response to pressure overload.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Myocardial samples from patients and animal models exhibiting myocardial hypertrophy were examined for SNO-MLP level using biotin-switch methods. SNO sites were further identified through liquid chromatography\u2013tandem mass spectrometry. Denitrosylation of MLP by the mutation of nitrosylation sites or overexpression of S-nitrosoglutathione reductase was used to analyze the contribution of SNO-MLP in myocardial hypertrophy. Downstream effectors of SNO-MLP were screened through mass spectrometry and confirmed by coimmunoprecipitation. Recruitment of TLR3 (Toll-like receptor 3) by SNO-MLP in myocardial hypertrophy was examined in TLR3 small interfering RNA\u2013transfected neonatal rat cardiomyocytes and in a TLR3 knockout mouse model.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>SNO-MLP level was significantly higher in hypertrophic myocardium from patients and in spontaneously hypertensive rats and mice subjected to transverse aortic constriction. The level of SNO-MLP also increased in angiotensin II\u2013 or phenylephrine-treated neonatal rat cardiomyocytes. S-nitrosylated site of MLP at cysteine 79 was identified by liquid chromatography\u2013tandem mass spectrometry and confirmed in neonatal rat cardiomyocytes. Mutation of cysteine 79 significantly reduced hypertrophic growth in angiotensin II\u2013 or phenylephrine-treated neonatal rat cardiomyocytes and transverse aortic constriction mice. Reducing SNO-MLP level by overexpression of S-nitrosoglutathione reductase greatly attenuated myocardial hypertrophy. Mechanistically, SNO-MLP stimulated TLR3 binding to MLP in response to hypertrophic stimuli, and disrupted this interaction by downregulating TLR3-attenuated myocardial hypertrophy. SNO-MLP also increased the complex formation between TLR3 and RIP3 (receptor-interacting protein kinase 3). This interaction in turn induced NLRP3 (nucleotide-binding oligomerization domain\u2013like receptor pyrin domain containing 3) inflammasome activation, thereby promoting the development of myocardial hypertrophy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Our findings revealed a key role of SNO-MLP in myocardial hypertrophy and demonstrated TLR3-mediated RIP3 and NLRP3 inflammasome activation as the downstream signaling pathway, which may represent a therapeutic target for myocardial hypertrophy and heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.119.042336","type":"journal-article","created":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T10:00:31Z","timestamp":1578304831000},"page":"984-1000","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":95,"title":["SNO-MLP (S-Nitrosylation of Muscle LIM Protein) Facilitates Myocardial Hypertrophy Through TLR3 (Toll-Like Receptor 3)\u2013Mediated RIP3 (Receptor-Interacting Protein Kinase 3) and NLRP3 (NOD-Like Receptor Pyrin Domain Containing 3) Inflammasome Activation"],"prefix":"10.1161","volume":"141","author":[{"given":"Xin","family":"Tang","sequence":"first","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Pan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feiyue","family":"Dai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglin","family":"Chao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesong","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengrong","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, the First Affiliated Hospital of Xiamen University, China (Z.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoliang","family":"Meng","sequence":"additional","affiliation":[{"name":"Nanjing Medical University, Nanjing, China (G.M.)."},{"name":"Department of Pharmacology, School of Pharmacy, Nantong University, China (G.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, China (C.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China (C.C., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China (C.C., J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, the University of Manchester, United Kingdom (X.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Ferro","sequence":"additional","affiliation":[{"name":"Cardiovascular Clinical Pharmacology, British Heart Foundation Centre of Research Excellence, Cardiovascular Division, King\u2019s College London, United Kingdom (A.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Lewis Kats School of Medicine, Temple University, Philadelphia, PA (H.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongshan","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanqing","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiulun","family":"Lu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Xie","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University, China (Y.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Ji","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Medical University, Nanjing, China (X.T., L.P., S.Z., F.D., M.C., H.J., X.L., Z.L., H.C., Y.G., Q.L., L.X., Y.J.)"},{"name":"State Key Laboratory of Reproductive Medicine (Y.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13882"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.06.001"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-011-0961-2"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.9.1553"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.03.036"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0092-8674(02)01226-6"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405488102"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M710277200"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cm.21106"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2015.04.077"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.165985"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12120"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.38319"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-012-0262-8"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.02.009"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00135.2017"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2018.03.034"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706796104"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.04.028"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312533"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvx130"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.041694"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13861"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.10.406"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2010.05.001"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2017.05.014"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4716"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000683"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4017"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.462341"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.732735"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.06.103"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307157"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00681.2015"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.313956"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.04.021"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1080\/10409238.2017.1304353"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.001974"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.2337\/db17-0223"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2014.906743"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.12.019"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00194.2014"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00230.2016"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1116302108"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.8.4942"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu146"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.310097"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0735-1097(01)01591-1"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0124-5"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.119.042336","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T08:36:24Z","timestamp":1715589384000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.119.042336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,24]]},"references-count":50,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,3,24]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.119.042336"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.119.042336","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,24]]},"assertion":[{"value":"2019-06-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}