{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:07:00Z","timestamp":1777529220820,"version":"3.51.4"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR002494"],"award-info":[{"award-number":["UL1TR002494"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0232507","type":"journal-article","created":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T13:47:50Z","timestamp":1594302470000},"page":"e0232507","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":31,"title":["Lack of sexual dimorphism in a mouse model of isoproterenol-induced cardiac dysfunction"],"prefix":"10.1371","volume":"15","author":[{"given":"Marianne K. O.","family":"Grant","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ibrahim Y.","family":"Abdelgawad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine A.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davis","family":"Seelig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-4185","authenticated-orcid":true,"given":"Beshay N.","family":"Zordoky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"issue":"1","key":"pone.0232507.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jacc.2017.04.052","article-title":"Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015","volume":"70","author":"GA Roth","year":"2017","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"pone.0232507.ref002","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/bph.12279","article-title":"Effects of biological sex on the pathophysiology of the heart","volume":"171","author":"L Fazal","year":"2014","journal-title":"Br J Pharmacol"},{"issue":"1","key":"pone.0232507.ref003","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1002\/ejhf.424","article-title":"Current state of knowledge on Takotsubo syndrome: a Position Statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology","volume":"18","author":"AR Lyon","year":"2016","journal-title":"Eur J Heart Fail"},{"issue":"1","key":"pone.0232507.ref004","first-page":"25","article-title":"Sex-dependent differences in clinical characteristics and in-hospital outcomes in patients with takotsubo syndrome","volume":"130","author":"M Budnik","year":"2020","journal-title":"Pol Arch Intern Med"},{"issue":"2","key":"pone.0232507.ref005","doi-asserted-by":"crossref","first-page":"140","DOI":"10.3904\/kjim.2015.30.2.140","article-title":"Microvascular angina: angina that predominantly affects women","volume":"30","author":"JJ Park","year":"2015","journal-title":"Korean J Intern Med"},{"issue":"47","key":"pone.0232507.ref006","doi-asserted-by":"crossref","first-page":"3859","DOI":"10.1093\/eurheartj\/ehz835","article-title":"Sex differences in heart failure","volume":"40","author":"CSP Lam","year":"2019","journal-title":"Eur Heart J"},{"issue":"2","key":"pone.0232507.ref007","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/s11897-015-0252-x","article-title":"Heart failure in women","volume":"12","author":"AL Taylor","year":"2015","journal-title":"Curr Heart Fail Rep"},{"issue":"1","key":"pone.0232507.ref008","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00021.2015","article-title":"Mechanistic Pathways of Sex Differences in Cardiovascular Disease","volume":"97","author":"V Regitz-Zagrosek","year":"2017","journal-title":"Physiol Rev"},{"issue":"8","key":"pone.0232507.ref009","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1161\/CIRCRESAHA.116.307509","article-title":"The Importance of Biological Sex and Estrogen in Rodent Models of Cardiovascular Health and Disease","volume":"118","author":"CL Blenck","year":"2016","journal-title":"Circ Res"},{"issue":"7","key":"pone.0232507.ref010","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1001\/jama.280.7.605","article-title":"Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen\/progestin Replacement Study (HERS) Research Group","volume":"280","author":"S Hulley","year":"1998","journal-title":"JAMA"},{"issue":"12","key":"pone.0232507.ref011","doi-asserted-by":"crossref","first-page":"4937","DOI":"10.1210\/en.2011-1212","article-title":"Aromatase deficiency confers paradoxical postischemic cardioprotection","volume":"152","author":"JR Bell","year":"2011","journal-title":"Endocrinology"},{"issue":"2","key":"pone.0232507.ref012","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.acvd.2011.12.002","article-title":"Testosterone improves cardiac function and alters angiotensin II receptors in isoproterenol-induced heart failure","volume":"105","author":"NN Kang","year":"2012","journal-title":"Arch Cardiovasc Dis"},{"issue":"1","key":"pone.0232507.ref013","first-page":"1057","article-title":"Influence of androgen on myocardial apoptosis and expression of myocardial IR and IRS1 in chronic heart failure rat models","volume":"17","author":"Y Wang","year":"2018","journal-title":"Mol Med Rep"},{"issue":"5","key":"pone.0232507.ref014","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1161\/ATVBAHA.116.307301","article-title":"Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases","volume":"37","author":"AP Arnold","year":"2017","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"11","key":"pone.0232507.ref015","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1038\/s41591-019-0643-8","article-title":"Sex differences in cardiometabolic disorders","volume":"25","author":"E Gerdts","year":"2019","journal-title":"Nat Med"},{"issue":"1","key":"pone.0232507.ref016","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13293-018-0198-2","article-title":"Clinical and preclinical evidence of sex-related differences in anthracycline-induced cardiotoxicity","volume":"9","author":"B Meiners","year":"2018","journal-title":"Biol Sex Differ"},{"issue":"3","key":"pone.0232507.ref017","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1097\/FJC.0000000000000506","article-title":"Prevention of betaeta-adrenergic-induced Adverse Cardiac Remodeling by Gonadectomy in Male but Not Female Spontaneously Hypertensive Rats","volume":"70","author":"M Magubane","year":"2017","journal-title":"J Cardiovasc Pharmacol"},{"issue":"2","key":"pone.0232507.ref018","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cardfail.2016.09.017","article-title":"Sex-Specific Effects of Adrenergic-Induced Left Ventricular Remodeling in Spontaneously Hypertensive Rats","volume":"23","author":"FS Michel","year":"2017","journal-title":"J Card Fail"},{"issue":"15","key":"pone.0232507.ref019","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1161\/01.CIR.0000144460.84795.E3","article-title":"Hypertrophy, fibrosis, and sudden cardiac death in response to pathological stimuli in mice with mutations in cardiac troponin T","volume":"110","author":"AH Maass","year":"2004","journal-title":"Circulation"},{"issue":"3","key":"pone.0232507.ref020","first-page":"146","article-title":"The influence of gender on cardiac fibrosis induced by sympathetic stimulation","volume":"51","author":"Y Hori","year":"2008","journal-title":"Chin J Physiol"},{"issue":"7","key":"pone.0232507.ref021","doi-asserted-by":"crossref","first-page":"H1423","DOI":"10.1152\/ajpheart.01211.2011","article-title":"Assessing left ventricular systolic dysfunction after myocardial infarction: are ejection fraction and dP\/dt(max) complementary or redundant?","volume":"302","author":"K Ishikawa","year":"2012","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"pone.0232507.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13293-016-0124-4","article-title":"Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl\/6 mice","volume":"8","author":"MK Grant","year":"2017","journal-title":"Biol Sex Differ"},{"key":"pone.0232507.ref023","article-title":"The interplay between genetic background and sexual dimorphism of doxorubicin-induced cardiotoxicity","volume":"2","author":"BN Zordoky","year":"2016","journal-title":"Cardiooncology"},{"issue":"1","key":"pone.0232507.ref024","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1161\/CIRCHEARTFAILURE.114.001180","article-title":"Sexual dimorphism of doxorubicin-mediated cardiotoxicity: potential role of energy metabolism remodeling","volume":"8","author":"M Moulin","year":"2015","journal-title":"Circ Heart Fail"},{"issue":"1","key":"pone.0232507.ref025","article-title":"Females Are Protected From Iron-Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress","volume":"6","author":"SK Das","year":"2017","journal-title":"J Am Heart Assoc"},{"issue":"5","key":"pone.0232507.ref026","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.cardfail.2009.12.017","article-title":"Gender differences in cardiac dysfunction and remodeling due to volume overload","volume":"16","author":"MR Dent","year":"2010","journal-title":"J Card Fail"},{"issue":"1","key":"pone.0232507.ref027","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/S0735-1097(99)00165-5","article-title":"Gender differences in molecular remodeling in pressure overload hypertrophy","volume":"34","author":"EO Weinberg","year":"1999","journal-title":"J Am Coll Cardiol"},{"issue":"25","key":"pone.0232507.ref028","doi-asserted-by":"crossref","first-page":"3187","DOI":"10.1161\/CIRCULATIONAHA.107.741702","article-title":"Cardiomyocyte overexpression of neuronal nitric oxide synthase delays transition toward heart failure in response to pressure overload by preserving calcium cycling","volume":"117","author":"X Loyer","year":"2008","journal-title":"Circulation"},{"issue":"17","key":"pone.0232507.ref029","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1161\/01.CIR.0000091403.62293.2B","article-title":"Phosphoinositide 3-kinase gamma-deficient mice are protected from isoproterenol-induced heart failure","volume":"108","author":"GY Oudit","year":"2003","journal-title":"Circulation"},{"issue":"1","key":"pone.0232507.ref030","doi-asserted-by":"crossref","first-page":"H30","DOI":"10.1152\/ajpheart.00636.2004","article-title":"Strain-dependent beta-adrenergic receptor function influences myocardial responses to isoproterenol stimulation in mice","volume":"289","author":"MD Faulx","year":"2005","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"4","key":"pone.0232507.ref031","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.bbrc.2016.12.033","article-title":"Lumican-null mice are susceptible to aging and isoproterenol-induced myocardial fibrosis","volume":"482","author":"SW Chen","year":"2017","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"pone.0232507.ref032","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.yexcr.2019.03.012","article-title":"MiR-1a-3p mitigates isoproterenol-induced heart failure by enhancing the expression of mitochondrial ND1 and COX1","volume":"378","author":"R He","year":"2019","journal-title":"Exp Cell Res"},{"issue":"3","key":"pone.0232507.ref033","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1530\/JOE-17-0613","article-title":"CRABP1 protects the heart from isoproterenol-induced acute and chronic remodeling","volume":"236","author":"SW Park","year":"2018","journal-title":"J Endocrinol"},{"issue":"3","key":"pone.0232507.ref034","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1097\/FJC.0000000000000652","article-title":"Contrasting Effects of Inhibition of Phosphodiesterase 3 and 5 on Cardiac Function and Interstitial Fibrosis in Rats With Isoproterenol-Induced Cardiac Dysfunction","volume":"73","author":"TM Nakata","year":"2019","journal-title":"J Cardiovasc Pharmacol"},{"key":"pone.0232507.ref035","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.yjmcc.2018.04.014","article-title":"QSOX1, a novel actor of cardiac protection upon acute stress in mice","volume":"119","author":"A Caillard","year":"2018","journal-title":"J Mol Cell Cardiol"},{"issue":"5","key":"pone.0232507.ref036","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1017\/S0007114508025075","article-title":"Sex differences in sensitivity to beta-adrenergic agonist isoproterenol in the isolated adult rat heart following prenatal protein restriction","volume":"101","author":"MJ Elmes","year":"2009","journal-title":"Br J Nutr"},{"issue":"5","key":"pone.0232507.ref037","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1097\/HJH.0000000000001266","article-title":"Race and sex differences in cardiovascular alpha-adrenergic and beta-adrenergic receptor responsiveness in men and women with high blood pressure","volume":"35","author":"A Sherwood","year":"2017","journal-title":"J Hypertens"},{"issue":"1","key":"pone.0232507.ref038","doi-asserted-by":"crossref","first-page":"H256","DOI":"10.1152\/ajpheart.2002.282.1.H256","article-title":"Mechanisms of sex differences in rat cardiac myocyte response to beta-adrenergic stimulation","volume":"282","author":"VM Vizgirda","year":"2002","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"2 Pt 2","key":"pone.0232507.ref039","first-page":"II36","article-title":"Effect of age, sex, and body surface area on echocardiographic left ventricular wall mass in normal subjects","volume":"9","author":"JM Gardin","year":"1987","journal-title":"Hypertension"},{"issue":"10","key":"pone.0232507.ref040","doi-asserted-by":"crossref","first-page":"527","DOI":"10.2459\/JCM.0000000000000696","article-title":"Sex-specific echocardiographic reference values: the women\u2019s point of view","volume":"19","author":"M Petitto","year":"2018","journal-title":"J Cardiovasc Med (Hagerstown)"},{"issue":"9","key":"pone.0232507.ref041","doi-asserted-by":"crossref","first-page":"4480","DOI":"10.1210\/en.2012-1353","article-title":"Estrogens mediate cardiac hypertrophy in a stimulus-dependent manner","volume":"153","author":"CD Haines","year":"2012","journal-title":"Endocrinology"},{"issue":"5","key":"pone.0232507.ref042","doi-asserted-by":"crossref","first-page":"R835","DOI":"10.1152\/ajpregu.00231.2016","article-title":"Sex-specific differences in age-dependent progression of aortic dysfunction and related cardiac remodeling in spontaneously hypertensive rats","volume":"312","author":"S Al-Gburi","year":"2017","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"3","key":"pone.0232507.ref043","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1161\/HYPERTENSIONAHA.115.06161","article-title":"Inhibition of Galectin-3 Pathway Prevents Isoproterenol-Induced Left Ventricular Dysfunction and Fibrosis in Mice","volume":"67","author":"G Vergaro","year":"2016","journal-title":"Hypertension"},{"issue":"1","key":"pone.0232507.ref044","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1161\/CIRCHEARTFAILURE.112.971168","article-title":"Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis","volume":"6","author":"L Yu","year":"2013","journal-title":"Circ Heart Fail"},{"issue":"5","key":"pone.0232507.ref045","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.ajpath.2015.12.017","article-title":"Myocardial Galectin-3 Expression Is Associated with Remodeling of the Pressure-Overloaded Heart and May Delay the Hypertrophic Response without Affecting Survival, Dysfunction, and Cardiac Fibrosis","volume":"186","author":"O Frunza","year":"2016","journal-title":"Am J Pathol"},{"issue":"1","key":"pone.0232507.ref046","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1038\/s41467-020-16584-z","article-title":"Core functional nodes and sex-specific pathways in human ischaemic and dilated cardiomyopathy","volume":"11","author":"M Li","year":"2020","journal-title":"Nat Commun"},{"issue":"6","key":"pone.0232507.ref047","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1097\/FJC.0000000000000081","article-title":"Impact of castration on changes in left ventricular diastolic pressure-volume relations induced by chronic adrenergic stimulation in rats","volume":"63","author":"B Hodson","year":"2014","journal-title":"J Cardiovasc Pharmacol"},{"issue":"5","key":"pone.0232507.ref048","doi-asserted-by":"crossref","first-page":"e0127515","DOI":"10.1371\/journal.pone.0127515","article-title":"Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity, Hypertrophy and Cardiac Contractility in Spontaneously Hypertensive Rats","volume":"10","author":"PL Dalpiaz","year":"2015","journal-title":"PLoS One"},{"issue":"1\u20132","key":"pone.0232507.ref049","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1023\/A:1025438000942","article-title":"Gender mediated cardiac protection from adverse ventricular remodeling is abolished by ovariectomy","volume":"251","author":"GL Brower","year":"2003","journal-title":"Mol Cell Biochem"},{"issue":"3","key":"pone.0232507.ref050","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.yjmcc.2008.11.018","article-title":"Estrogen exerts concentration-dependent pro-and anti-hypertrophic effects on adult cultured ventricular myocytes. Role of NHE-1 in estrogen-induced hypertrophy","volume":"46","author":"A Kilic","year":"2009","journal-title":"J Mol Cell Cardiol"},{"issue":"3","key":"pone.0232507.ref051","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.cardfail.2007.10.024","article-title":"17 Beta-estradiol differentially affects left ventricular and cardiomyocyte hypertrophy following myocardial infarction and pressure overload","volume":"14","author":"RD Patten","year":"2008","journal-title":"J Card Fail"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0232507","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T13:48:52Z","timestamp":1594302532000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0232507"}},"subtitle":[],"editor":[{"given":"Vincenzo","family":"Lionetti","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2020,7,9]]},"references-count":51,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,7,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0232507","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.04.17.046417","asserted-by":"object"}]},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,9]]}}}