{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:50:55Z","timestamp":1791474655902,"version":"4.3.4"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2017YFC1702003"],"award-info":[{"award-number":["2017YFC1702003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Heilongjiang Outstanding Youth Science Fund","award":["JJ2017JQ0035"],"award-info":[{"award-number":["JJ2017JQ0035"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570399"],"award-info":[{"award-number":["81570399"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773735"],"award-info":[{"award-number":["81773735"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81800399"],"award-info":[{"award-number":["81800399"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Metoprolol is regarded as a first-line medicine for the treatment of myocardial infarction (MI). However, the underlying mechanisms remain largely unknown. This study aimed to investigate the involvement of miR-1 in the pharmacological function of metoprolol.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In vivo MI model was established by left anterior descending coronary artery (LAD) ligation. The effects of metoprolol on infarct size and cardiac dysfunction were determined by triphenyltetrazolium chloride staining and cardiac echocardiography, respectively. In vitro oxidative stress cardiomyocyte model was established by H2O2 treatment. The effect of metoprolol on the expression of miR-1 and connexin43 (Cx43) was quantified by real-time PCR and western blot, respectively. The intercellular communication was evaluated by lucifer yellow dye diffusion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>Left anterior descending ligation-induced MI injury was markedly attenuated by metoprolol as shown by reduced infarct size and better cardiac function. Metoprolol reversed the up-regulation of miR-1 and down-regulation of Cx43 in MI heart. Moreover, in H2O2-stimulated cardiomyocytes, overexpression of miR-1 abolished the effects of metoprolol on Cx43 up-regulation and increased intercellular communication, indicating that miR-1 may be a necessary mediator for the cardiac protective function of metoprolol.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Metoprolol relieves MI injury via suppression miR-1, thus increasing its target protein Cx43 and improving intercellular communication.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.13192","type":"journal-article","created":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T13:09:21Z","timestamp":1573218561000},"page":"76-83","source":"Crossref","is-referenced-by-count":16,"title":["Metoprolol protects against myocardial infarction by inhibiting miR-1 expression in rats"],"prefix":"10.1093","volume":"72","author":[{"given":"Wei","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University , Harbin,","place":["China"]},{"name":"School of Pharmacy, Jining Medical University , Rizhao,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longyin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University , Harbin,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhange","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University , Harbin,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University , Harbin,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University , Harbin,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University , Harbin,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University , Harbin,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqian","family":"Xu","sequence":"additional","affiliation":[{"name":"Mudanjiang Medical University , Mudanjiang,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8754-8938","authenticated-orcid":false,"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University , Harbin,","place":["China"]},{"name":"Institute of Cardiovascular Research, Harbin Medical University , Harbin,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2024103012354673100_jphp13192-cit-0001","doi-asserted-by":"crossref","first-page":"163","DOI":"10.4330\/wjc.v8.i2.163","article-title":"Micromanaging cardiac regeneration: targeted delivery of microRNAs for cardiac repair and regeneration","volume":"2","author":"Kamps","year":"2016","journal-title":"World J Cardiol"},{"key":"2024103012354673100_jphp13192-cit-0002","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41440-019-0220-z","article-title":"Absolute risk score for stroke, myocardial infarction, and all cardiovascular disease: Japan Arteriosclerosis Longitudinal Study","volume":"4","author":"Harada","year":"2019","journal-title":"Hypertens Res"},{"key":"2024103012354673100_jphp13192-cit-0003","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ahj.2018.09.016","article-title":"The appropriateness of coronary investigation in myocardial injury and type 2 myocardial infarction (ACT-2): a randomized trial design","volume":"208","author":"Lambrakis","year":"2019","journal-title":"Am Heart J"},{"key":"2024103012354673100_jphp13192-cit-0004","first-page":"4114","article-title":"Effects of early intravenous low-dose of metoprolol on cardiac sympathetic activities and electrophysiological properties in myocardial infarction heart","volume":"5","author":"Wang","year":"2018","journal-title":"Exp Ther Med"},{"key":"2024103012354673100_jphp13192-cit-0005","doi-asserted-by":"crossref","first-page":"664","DOI":"10.3389\/fphys.2018.00664","article-title":"MicroRNA-1 and circulating microvesicles mediate the protective effects of dantonic in acute myocardial infarction rat models","volume":"9","author":"Sun","year":"2018","journal-title":"Front Physiol"},{"key":"2024103012354673100_jphp13192-cit-0006","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1161\/CIRCRESAHA.110.227421","article-title":"Enhanced fibroblast-myocyte interactions in response to cardiac injury","volume":"8","author":"Vasquez","year":"2010","journal-title":"Circ Res"},{"key":"2024103012354673100_jphp13192-cit-0007","doi-asserted-by":"crossref","first-page":"3619","DOI":"10.1242\/jcs.200667","article-title":"Role of connexin 43 in different forms of intercellular communication \u2013 gap junctions, extracellular vesicles and tunnelling nanotubes","volume":"21","author":"Ribeiro-Rodrigues","year":"2017","journal-title":"J Cell Sci"},{"key":"2024103012354673100_jphp13192-cit-0008","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1093\/cvr\/cvp232","article-title":"MicroRNA-1 downregulation by propranolol in a rat model of myocardial infarction: a new mechanism for ischaemic cardioprotection","volume":"3","author":"Lu","year":"2009","journal-title":"Cardiovasc Res"},{"key":"2024103012354673100_jphp13192-cit-0009","doi-asserted-by":"crossref","first-page":"7145","DOI":"10.1038\/s41598-018-25147-8","article-title":"Overexpression of Cx43 in cells of the myocardial scar: correction of post-infarct arrhythmias through heterotypic cell-cell coupling","volume":"8","author":"Roell","year":"2018","journal-title":"Sci Rep"},{"key":"2024103012354673100_jphp13192-cit-0010","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.yjmcc.2014.07.009","article-title":"beta-Blocker carvedilol protects cardiomyocytes against oxidative stress-induced apoptosis by up-regulating miR-133 expression","volume":"75","author":"Xu","year":"2014","journal-title":"J Mol Cell Cardiol"},{"key":"2024103012354673100_jphp13192-cit-0011","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2014.430","article-title":"MicroRNA-30d regulates cardiomyocyte pyroptosis by directly targeting foxo3a in diabetic cardiomyopathy","volume":"5","author":"Li","year":"2014","journal-title":"Cell Death Dis"},{"key":"2024103012354673100_jphp13192-cit-0012","doi-asserted-by":"crossref","first-page":"9401","DOI":"10.1038\/srep09401","article-title":"MicroRNA-26a prevents endothelial cell apoptosis by directly targeting TRPC6 in the setting of atherosclerosis","volume":"5","author":"Zhang","year":"2015","journal-title":"Sci Rep"},{"key":"2024103012354673100_jphp13192-cit-0013","doi-asserted-by":"crossref","first-page":"5559","DOI":"10.1111\/bph.13002","article-title":"Genistein alleviates pressure overload-induced cardiac dysfunction and interstitial fibrosis in mice","volume":"172","author":"Qin","year":"2015","journal-title":"Br J Pharmacol"},{"key":"2024103012354673100_jphp13192-cit-0014","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.ijcard.2019.07.082","article-title":"SIRT6-mediated transcriptional suppression of MALAT1 is a key mechanism for endothelial to mesenchymal transition","volume":"295","author":"Qin","year":"2019","journal-title":"Int J Cardiol"},{"key":"2024103012354673100_jphp13192-cit-0015","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ijcard.2017.06.054","article-title":"Diagnostic and prognostic value of miR-1 and miR-29b on adverse ventricular remodeling after acute myocardial infarction \u2013 The SITAGRAMI-miR analysis","volume":"244","author":"Grabmaier","year":"2017","journal-title":"Int J Cardiol"},{"key":"2024103012354673100_jphp13192-cit-0016","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nm1569","article-title":"The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2","volume":"13","author":"Yang","year":"2007","journal-title":"Nat Med"},{"key":"2024103012354673100_jphp13192-cit-0017","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1177\/1074248418801567","article-title":"The protective effects of preconditioning with dioscin on myocardial ischemia\/reperfusion-induced ventricular arrhythmias by increasing connexin 43 expression in rats","volume":"24","author":"Cheng","year":"2019","journal-title":"J Cardiovasc Pharmacol Ther"},{"key":"2024103012354673100_jphp13192-cit-0018","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1161\/CIRCRESAHA.118.313835","article-title":"Adrenomedullin induces cardiac lymphangiogenesis after myocardial infarction and regulates cardiac edema via connexin 43","volume":"124","author":"Trincot","year":"2019","journal-title":"Circ Res"},{"key":"2024103012354673100_jphp13192-cit-0019","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/15701611113119990003","article-title":"Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction","volume":"1","author":"Neri","year":"2015","journal-title":"Curr Vasc Pharmacol"},{"key":"2024103012354673100_jphp13192-cit-0020","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1159\/000480317","article-title":"Exosomes derived from mesenchymal stem cells rescue myocardial ischaemia\/reperfusion injury by inducing cardiomyocyte autophagy via AMPK and Akt pathways","volume":"43","author":"Liu","year":"2017","journal-title":"Cell Physiol Biochem"},{"key":"2024103012354673100_jphp13192-cit-0021","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/s12028-017-0423-6","article-title":"Dobutamine, a beta1 adrenoceptor agonist, increases cerebral oxygenation during acute anemia and apneic hypoxia","volume":"3","author":"Kurita","year":"2017","journal-title":"Neurocrit Care"},{"key":"2024103012354673100_jphp13192-cit-0022","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1093\/cvr\/cvu192","article-title":"Inhibition of a TREK-like K+ channel current by noradrenaline requires both beta1- and beta2-adrenoceptors in rat atrial myocytes","volume":"1","author":"Bond","year":"2014","journal-title":"Cardiovasc Res"},{"key":"2024103012354673100_jphp13192-cit-0023","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.3389\/fphys.2018.01383","article-title":"Profibrotic, electrical, and calcium-handling remodeling of the atria in heart failure patients with and without atrial fibrillation","volume":"9","author":"Molina","year":"2018","journal-title":"Front Physiol"},{"key":"2024103012354673100_jphp13192-cit-0024","first-page":"1082","article-title":"2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation","volume":"12","author":"Ibanez","year":"2017","journal-title":"Rev Esp Cardiol (Engl Ed)"},{"key":"2024103012354673100_jphp13192-cit-0025","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1007\/s11596-012-1033-3","article-title":"High-frequency ultrasound evaluation of effects of early treatment with metoprolol on myocardial inflammatory cytokine expression in rats with acute myocardial infarction","volume":"5","author":"Wu","year":"2012","journal-title":"J Huazhong Univ Sci Technolog Med Sci"},{"key":"2024103012354673100_jphp13192-cit-0026","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000351074","article-title":"Metoprolol-mediated amelioration of sympathetic nerve sprouting after myocardial infarction","volume":"126","author":"Wang","year":"2013","journal-title":"Cardiology"},{"key":"2024103012354673100_jphp13192-cit-0027","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s12013-012-9428-0","article-title":"The effect of c-fos on acute myocardial infarction and the significance of metoprolol intervention in a rat model","volume":"65","author":"Zhang","year":"2013","journal-title":"Cell Biochem Biophys"},{"key":"2024103012354673100_jphp13192-cit-0028","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1159\/000324012","article-title":"Tanshinone IIA inhibits miR-1 expression through p38 MAPK signal pathway in post-infarction rat cardiomyocytes","volume":"26","author":"Zhang","year":"2010","journal-title":"Cell Physiol Biochem"},{"key":"2024103012354673100_jphp13192-cit-0029","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s11010-015-2635-4","article-title":"CDK6 mediates the effect of attenuation of miR-1 on provoking cardiomyocyte hypertrophy","volume":"412","author":"Yuan","year":"2016","journal-title":"Mol Cell Biochem"},{"key":"2024103012354673100_jphp13192-cit-0030","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1039\/C5MB00806A","article-title":"The regulatory function of microRNA-1 in arrhythmias","volume":"2","author":"Liao","year":"2016","journal-title":"Mol Biosyst"},{"key":"2024103012354673100_jphp13192-cit-0031","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.acvd.2015.07.003","article-title":"Circulating microribonucleic acids miR-1, miR-21 and miR-208a in patients with symptomatic heart failure: preliminary results","volume":"108","author":"Sygitowicz","year":"2015","journal-title":"Arch Cardiovasc Dis"},{"key":"2024103012354673100_jphp13192-cit-0032","doi-asserted-by":"crossref","first-page":"2798","DOI":"10.1016\/j.ijcard.2012.07.009","article-title":"Upregulation of microRNA-1 and microRNA-133 contributes to arsenic-induced cardiac electrical remodeling","volume":"167","author":"Shan","year":"2013","journal-title":"Int J Cardiol"},{"key":"2024103012354673100_jphp13192-cit-0033","doi-asserted-by":"crossref","first-page":"455","DOI":"10.7150\/ijbs.4630","article-title":"Overexpression of microRNA-1 causes atrioventricular block in rodents","volume":"5","author":"Zhang","year":"2013","journal-title":"Int J Biol Sci"},{"key":"2024103012354673100_jphp13192-cit-0034","first-page":"1","article-title":"Effect of wenxin granules on gap junction and MiR-1 in rats with myocardial infarction","volume":"5","author":"Wu","year":"2017","journal-title":"Biomed Res Int"},{"key":"2024103012354673100_jphp13192-cit-0035","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cell.2005.10.022","article-title":"Human RISC couples microRNA biogenesis and posttranscriptional gene silencing","volume":"123","author":"Gregory","year":"2005","journal-title":"Cell"},{"key":"2024103012354673100_jphp13192-cit-0036","doi-asserted-by":"crossref","first-page":"10206","DOI":"10.1038\/s41598-018-28562-z","article-title":"Comparison between renal denervation and metoprolol on the susceptibility of ventricular arrhythmias in rats with myocardial infarction","volume":"8","author":"Jiang","year":"2018","journal-title":"Sci Rep"},{"key":"2024103012354673100_jphp13192-cit-0037","first-page":"1902","article-title":"Metoprolol protects cardiomyocytes in rabbit model of heart failure by regulating Cx43","volume":"2","author":"Zhai","year":"2018","journal-title":"Exp Ther Med"},{"key":"2024103012354673100_jphp13192-cit-0038","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1111\/jce.13802","article-title":"Selective ablation of ligament of Marshall inhibits ventricular arrhythmias during acute myocardial infarction: possible mechanisms","volume":"30","author":"Yu","year":"2018","journal-title":"J Cardiovasc Electrophysiol"},{"key":"2024103012354673100_jphp13192-cit-0039","first-page":"5283","article-title":"Telmisartan reduces arrhythmias through increasing cardiac connexin43 by inhibiting IL-17 after myocardial infarction in rats","volume":"22","author":"Chang","year":"2017","journal-title":"Eur Rev Med Pharmacol Sci"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjphp.13192","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jphp.13192","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jphp.13192","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/72\/1\/76\/60227037\/jphp13192.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/72\/1\/76\/60227037\/jphp13192.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T18:05:39Z","timestamp":1730311539000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/72\/1\/76\/6122116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,1]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1,1]]},"published-print":{"date-parts":[[2020,1,1]]}},"URL":"https:\/\/doi.org\/10.1111\/jphp.13192","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,1]]},"published":{"date-parts":[[2020,1,1]]}}}