{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:46:37Z","timestamp":1791999997484,"version":"4.4.0"},"reference-count":51,"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\">\n              Fetal growth impacts cardiovascular health throughout postnatal life in humans. Various animal models of intrauterine growth restriction exhibit reduced heart size at birth, which negatively influences cardiac function in adulthood. The mechanistic target of rapamycin complex 1 (m\n              <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>\n              1) integrates nutrient and growth factor availability with cell growth, thereby regulating organ size. This study aimed at elucidating a possible involvement of m\n              <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>\n              1 in intrauterine growth restriction and prenatal heart growth.\n            <\/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              We inhibited m\n              <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>\n              1 in fetal mice by rapamycin treatment of pregnant dams in late gestation. Prenatal rapamycin treatment reduces m\n              <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>\n              1 activity in various organs at birth, which is fully restored by postnatal day 3. Rapamycin\u2010treated neonates exhibit a 16% reduction in body weight compared with vehicle\u2010treated controls. Heart weight decreases by 35%, resulting in a significantly reduced heart weight\/body weight ratio, smaller left ventricular dimensions, and reduced cardiac output in rapamycin\u2010 versus vehicle\u2010treated mice at birth. Although proliferation rates in neonatal rapamycin\u2010treated hearts are unaffected, cardiomyocyte size is reduced, and apoptosis increased compared with vehicle\u2010treated neonates. Rapamycin\u2010treated mice exhibit postnatal catch\u2010up growth, but body weight and left ventricular mass remain reduced in adulthood. Prenatal m\n              <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>\n              1 inhibition causes a reduction in cardiomyocyte number in adult hearts compared with controls, which is partially compensated for by an increased cardiomyocyte volume, resulting in normal cardiac function without maladaptive left ventricular remodeling.\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              Prenatal rapamycin treatment of pregnant dams represents a new mouse model of intrauterine growth restriction and identifies an important role of m\n              <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>\n              1 in perinatal cardiac growth.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.005506","type":"journal-article","created":{"date-parts":[[2017,8,5]],"date-time":"2017-08-05T00:10:27Z","timestamp":1501891827000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Prenatal Mechanistic Target of Rapamycin Complex 1 (m TORC1) Inhibition by Rapamycin Treatment of Pregnant Mice Causes Intrauterine Growth Restriction and Alters Postnatal Cardiac Growth, Morphology, and Function"],"prefix":"10.1161","volume":"6","author":[{"given":"Maria","family":"Hennig","sequence":"first","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Fiedler","sequence":"additional","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Jux","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, University Hospital M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludwig","family":"Thierfelder","sequence":"additional","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg\u2010Detlef","family":"Drenckhahn","sequence":"additional","affiliation":[{"name":"Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine, Berlin, Germany"},{"name":"Department of Pediatric Cardiology, University Hospital M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00040"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20091861"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1017\/S2040174415001300"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2763"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.03.003"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302022"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.04.011"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.08.046"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054221"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.423640"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2008.09.005"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv028"},{"key":"e_1_3_5_14_2","first-page":"431","article-title":"Efficient Cre\u2010mediated deletion in cardiac progenitor cells conferred by a 3\u2032UTR\u2010ires\u2010Cre allele of the homeobox gene Nkx2\u20105","volume":"46","author":"Stanley EG","year":"2002","unstructured":"Stanley EG, Biben C, Elefanty A, Barnett L, Koentgen F, Robb L, Harvey RP. 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