{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:20:14Z","timestamp":1790713214414,"version":"4.1.0"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,1,11]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Sex\u2010related differences in cardiac function and iron metabolism exist in humans and experimental animals. Male patients and preclinical animal models are more susceptible to cardiomyopathies and heart failure. However, whether similar differences are seen in iron\u2010overload cardiomyopathy is poorly understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Male and female wild\u2010type and hemojuvelin\u2010null mice were injected and fed with a high\u2010iron diet, respectively, to develop secondary iron overload and genetic hemochromatosis. Female mice were completely protected from iron\u2010overload cardiomyopathy, whereas iron overload resulted in marked diastolic dysfunction in male iron\u2010overloaded mice based on echocardiographic and invasive pressure\u2010volume analyses. Female mice demonstrated a marked suppression of iron\u2010mediated oxidative stress and a lack of myocardial fibrosis despite an equivalent degree of myocardial iron deposition. Ovariectomized female mice with iron overload exhibited essential pathophysiological features of iron\u2010overload cardiomyopathy showing distinct diastolic and systolic dysfunction, severe myocardial fibrosis, increased myocardial oxidative stress, and increased expression of cardiac disease markers. Ovariectomy prevented iron\u2010induced upregulation of ferritin, decreased myocardial\n              <jats:styled-content style=\"fixed-case\">SERCA<\/jats:styled-content>\n              2a levels, and increased\n              <jats:styled-content style=\"fixed-case\">NCX<\/jats:styled-content>\n              1 levels. 17\u03b2\u2010Estradiol therapy rescued the iron\u2010overload cardiomyopathy in male wild\u2010type mice. The responses in wild\u2010type and hemojuvelin\u2010null female mice were remarkably similar, highlighting a conserved mechanism of sex\u2010dependent protection from iron\u2010overload\u2010mediated cardiac injury.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Male and female mice respond differently to iron\u2010overload\u2010mediated effects on heart structure and function, and females are markedly protected from iron\u2010overload cardiomyopathy. Ovariectomy in female mice exacerbated iron\u2010induced myocardial injury and precipitated severe cardiac dysfunction during iron\u2010overload conditions, whereas 17\u03b2\u2010estradiol therapy was protective in male iron\u2010overloaded mice.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.003456","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T02:15:26Z","timestamp":1485224126000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":45,"title":["Females Are Protected From Iron\u2010Overload Cardiomyopathy Independent of Iron Metabolism: Key Role of Oxidative Stress"],"prefix":"10.1161","volume":"6","author":[{"given":"Subhash K.","family":"Das","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada"},{"name":"Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, 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