{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T08:23:32Z","timestamp":1775982212895,"version":"3.50.1"},"reference-count":76,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,8,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Heart failure preceded by hypertrophy is a leading cause of death, and sex differences in hypertrophy are well known, although the basis for these sex differences 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              This study used a systems biology approach to investigate mechanisms underlying sex differences in cardiac hypertrophy. Male and female mice were treated for 2 and 3\u00a0weeks with angiotensin\n              <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n              to induce hypertrophy. Sex differences in cardiac hypertrophy were apparent after 3\u00a0weeks of treatment.\n              <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n              sequencing was performed on hearts, and sex differences in\n              <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n              expression at baseline and following hypertrophy were observed, as well as within\u2010sex differences between baseline and hypertrophy. Sex differences in\n              <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n              were substantial at baseline and reduced somewhat with hypertrophy, as the\n              <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n              differences induced by hypertrophy tended to overwhelm the sex differences. We performed an integrative analysis to identify\n              <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n              networks that were differentially regulated in the 2 sexes by hypertrophy and obtained a network centered on\n              <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n              \u03b1 (peroxisome proliferator\u2010activated receptor \u03b1). Mouse experiments further showed that acute inhibition of\n              <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n              \u03b1 blocked sex differences in the development of hypertrophy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The data in this study suggest that\n              <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\n              \u03b1 is involved in the sex\u2010dimorphic regulation of cardiac hypertrophy.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.005838","type":"journal-article","created":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T18:25:38Z","timestamp":1504290338000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["A Systems Biology Approach to Investigating 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