{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:01:46Z","timestamp":1791291706755,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T00:00:00Z","timestamp":1549497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["UMO-2016\/23\/B\/NZ3\/03151"],"award-info":[{"award-number":["UMO-2016\/23\/B\/NZ3\/03151"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoxic injury of cardiovascular system is one of the most frequent complications following ischaemia. Heart injury arises from increased degradation of contractile proteins, such as myosin light chains (MLCs) and troponin I by matrix metalloproteinase 2 (MMP\u20102). The aim of the current research was to study the effects of 5\u2010phenyloxyphenyl\u20105\u2010aminoalkyl nitrate barbiturate (MMP\u20102\u2010inhibitor\u2010NO\u2010donor hybrid) on hearts subjected to ischaemia\/reperfusion (I\/R) injury. Primary human cardiac myocytes and Wistar rat hearts perfused using Langendorff method have been used. Human cardiomyocytes or rat hearts were subjected to I\/R in the presence or absence of tested hybrid. Haemodynamic parameters of heart function, markers of I\/R injury, gene and protein expression of MMP\u20102, MMP\u20109, inducible form of NOS (iNOS), asymmetric dimethylarginine (ADMA), as well as MMP\u20102 activity were measured. Mechanical heart function, coronary flow (CF) and heart rate (HR) were decreased in hearts subjected to I\/R Treatment of hearts with the hybrid (1\u201010\u00a0\u00b5mol\/L) resulted in a concentration\u2010dependent recovery of mechanical function, improved CF and HR. This improvement was associated with decreased tissue injury and reduction of synthesis and activity of MMP\u20102. Decreased activity of intracellular MMP\u20102 led to reduced degradation of MLC and improved myocyte contractility in a concentration\u2010dependent manner. An infusion of a MMP\u20102\u2010inhibitor\u2010NO\u2010donor hybrid into I\/R hearts decreased the expression of iNOS and reduced the levels of ADMA. Thus, 5\u2010phenyloxyphenyl\u20105\u2010aminoalkyl nitrate barbiturate protects heart from I\/R injury.<\/jats:p>","DOI":"10.1111\/jcmm.14191","type":"journal-article","created":{"date-parts":[[2019,2,7]],"date-time":"2019-02-07T09:43:39Z","timestamp":1549532619000},"page":"2836-2848","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Cardioprotective effect of MMP\u20102\u2010inhibitor\u2010NO\u2010donor hybrid against ischaemia\/reperfusion injury"],"prefix":"10.1111","volume":"23","author":[{"given":"Anna","family":"Krzywonos\u2010Zawadzka","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry Wroclaw Medical University Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Franczak","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry Wroclaw Medical University Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Olejnik","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry Wroclaw Medical University Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Radomski","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine University of Saskatchewan Saskatoon Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Gilmer","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences Trinity College Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Sawicki","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry Wroclaw Medical University Wroclaw Poland"},{"name":"Department of Anatomy, Physiology and Pharmacology, College of Medicine University of Saskatchewan Saskatoon Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mieczys\u0142aw","family":"Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry Wroclaw Medical University Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2769-0166","authenticated-orcid":false,"given":"Iwona","family":"Bil\u2010Lula","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Diagnostics, Division of Clinical Chemistry Wroclaw Medical University Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,7]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"214","article-title":"Oxidative stress and heart failure","volume":"96","author":"Byrne JA","year":"2003","journal-title":"Arch Mal Coeur Vaiss"},{"key":"e_1_2_7_3_1","first-page":"774","article-title":"The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge","volume":"38","author":"Heusch G","year":"2017","journal-title":"Eur Heart J"},{"key":"e_1_2_7_4_1","first-page":"935","article-title":"Targeting reperfusion injury in patients with ST\u2010segment elevation myocardial infarction: trials and tribulations","volume":"38","author":"Hausenloy DJ","year":"2017","journal-title":"Eur Heart J"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.01.024"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2005.10.008"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.11.004"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-9842(99)00048-3"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000028818.33488.7B"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3181e14f1d"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2012.08622.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.930222"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.531616"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(01)00445-X"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12827"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.15.1833"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071794"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/heart.85.3.342"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199204002-00018"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1006\/niox.2001.0337"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.038034"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01034.2009"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.2.454"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm201352k"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00335.2017"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-018-0696-8"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(80)90338-3"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2010.03.032"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394309-5.00006-7"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01094.x"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-014-0424-y"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.06.055"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-009-0035-1"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI62874"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra071667"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2007"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000065603.09430.58"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.82.4.482"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.2147\/VHRM.S68415"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.155439"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.07.055"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00719-8"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-290-2_7"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-012-1131-1"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568010033484098"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2006.11.005"},{"issue":"829","key":"e_1_2_7_47_1","first-page":"837a","article-title":"Nitric oxide synthases: regulation and function","volume":"33","author":"F\u00f6rstermann U","year":"2012","journal-title":"Eur Heart J"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2010.04.007"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(99)00184-7"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.46.29223"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000052990.68216.EF"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.19.6.2904"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0302SM"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161210794519246"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1177\/1358836X0501000103"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91481-4"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.72.2.403"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)01013-5"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-2317fje"},{"key":"e_1_2_7_60_1","first-page":"105","article-title":"Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis","volume":"33","author":"Miyazaki H","year":"1999","journal-title":"J Cardiol"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310820"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.14191","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.14191","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.14191","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T05:25:10Z","timestamp":1692681910000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.14191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,7]]},"references-count":60,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1111\/jcmm.14191"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.14191","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,7]]},"assertion":[{"value":"2018-11-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}