{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T01:27:52Z","timestamp":1790645272906,"version":"4.1.0"},"reference-count":55,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T00:00:00Z","timestamp":1489104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81473203"],"award-info":[{"award-number":["81473203"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cardiac hypertrophy is associated with autonomic imbalance, characterized by enhanced sympathetic activity and withdrawal of parasympathetic control. Increased parasympathetic function improves ventricular performance. However, whether pyridostigmine, a reversible acetylcholinesterase inhibitor, can offset cardiac hypertrophy induced by pressure overload remains unclear. Hence, this study aimed to determine whether pyridostigmine can ameliorate pressure overload\u2010induced cardiac hypertrophy and identify the underlying mechanisms. Rats were subjected to either sham or constriction of abdominal aorta surgery and treated with or without pyridostigmine for 8 weeks. Vagal activity and cardiac function were determined using PowerLab. Cardiac hypertrophy was evaluated using various histological stains. Protein markers for cardiac hypertrophy were quantitated by Western blot and immunoprecipitation. Pressure overload resulted in a marked reduction in vagal discharge and a profound increase in cardiac hypertrophy index and cardiac dysfunction. Pyridostigmine increased the acetylcholine levels by inhibiting acetylcholinesterase in rats with pressure overload. Pyridostigmine significantly attenuated cardiac hypertrophy based on reduction in left ventricular weight\/body weight, suppression of the levels of atrial natriuretic peptide, brain natriuretic peptide and \u03b2\u2010myosin heavy chain, and a reduction in cardiac fibrosis. These effects were accompanied by marked improvement of cardiac function. Additionally, pyridostigmine inhibited the CaN\/<jats:styled-content style=\"fixed-case\">NFAT<\/jats:styled-content>3\/<jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4 pathway and suppressed Orai1\/<jats:styled-content style=\"fixed-case\">STIM<\/jats:styled-content>1 complex formation. In conclusion, pressure overload resulted in cardiac hypertrophy, cardiac dysfunction and a significant reduction in vagal discharge. Pyridostigmine attenuated cardiac hypertrophy and improved cardiac function, which was related to improved cholinergic transmission efficiency (decreased acetylcholinesterase and increased acetylcholine), inhibition of the CaN\/<jats:styled-content style=\"fixed-case\">NFAT<\/jats:styled-content>3\/<jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4 pathway and suppression of the interaction of Orai1\/<jats:styled-content style=\"fixed-case\">STIM<\/jats:styled-content>1.<\/jats:p>","DOI":"10.1111\/jcmm.13133","type":"journal-article","created":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T15:02:51Z","timestamp":1489158171000},"page":"2106-2116","source":"Crossref","is-referenced-by-count":22,"title":["Long\u2010term administration of pyridostigmine attenuates pressure overload\u2010induced cardiac hypertrophy by inhibiting calcineurin signalling"],"prefix":"10.1111","volume":"21","author":[{"given":"Yi","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xian Jiaotong University Health Science Center Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xian Jiaotong University Health Science Center Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xian Jiaotong University Health Science Center Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xian Jiaotong University Health Science Center Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Jiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xian Jiaotong University Health Science Center Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long\u2010Zhu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xian Jiaotong University Health Science Center Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xian Jiaotong University Health Science Center Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Na","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xian Jiaotong University Health Science Center Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Jin","family":"Zang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medical Sciences Xian Jiaotong University Health Science Center Xi'an Shaanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.157"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.03699"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.17116\/sudmed20155839-11"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13010"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000105721.71640.DA"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2008.07.016"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20030064"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2004.05.002"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0100-879X2002000600008"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000062"},{"key":"e_1_2_7_12_1","first-page":"5159","article-title":"Complications of image\u2010guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver","volume":"30","author":"Poggi G","year":"2010","journal-title":"Anticancer Res"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81573-1"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000371454"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.112.967489"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu068"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.01.020"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2625"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.578492"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000020689.12472.E0"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/17453678008990848"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-010-0089-z"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2013.07.002"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2014.08.009"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/17.suppl_F.16"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/02688697.2012.732716"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hrthm.2015.11.031"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/heart.89.8.854"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2008.10.018"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0066-782X1999000300003"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-196205000-00012"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12121"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104476"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(91)90117-L"},{"key":"e_1_2_7_35_1","first-page":"2618","article-title":"Mechanisms of muscarinic modulation of protein phosphorylation in intact ventricles","volume":"43","author":"Watanabe AM","year":"1984","journal-title":"Fed Proc"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.3.274"},{"key":"e_1_2_7_37_1","first-page":"H713","article-title":"Peripheral muscarinic control of norepinephrine release in the cardiovascular system","volume":"239","author":"Muscholl E","year":"1980","journal-title":"Am J Physiol"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2004.05.002"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39778"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00996-09"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.13-238279"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0100179"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-277046"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autneu.2013.07.001"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpv017"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00638.2012"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370213520109"},{"key":"e_1_2_7_48_1","first-page":"339","article-title":"Induction and analysis of cardiac hypertrophy in transgenic animal models","volume":"112","author":"Barbosa ME","year":"2005","journal-title":"Methods Mol Med"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.110.957969"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.184051"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.08.005"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.2.4.6705"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2011.11.003"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu207"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.031229"},{"key":"e_1_2_7_56_1","article-title":"Improving vagal activity ameliorates cardiac fibrosis induced by angiotensin II: in vivo and in vitro","volume":"5","author":"Liu JJ","year":"2015","journal-title":"Sci Rep"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.13133","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.13133","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,22]],"date-time":"2023-09-22T19:45:48Z","timestamp":1695411948000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.13133"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,10]]},"references-count":55,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2017,9]]}},"alternative-id":["10.1111\/jcmm.13133"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.13133","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,10]]}}}