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This study was to determine whether Flt3 activation could ameliorate pressure overload\u2010induced heart hypertrophy and fibrosis, and to elucidate the mechanisms of action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vivo cardiac hypertrophy and remodelling experiments were conducted by infusing angiotensin II (Ang II) chronically in male C57BL\/6 mice. Flt3\u2010specific ligand (FL) was administered intraperitoneally every two days (5\u00a0\u00b5g\/mouse). In vitro experiments on hypertrophy, apoptosis and autophagy mechanism were performed in neonatal rat cardiomyocytes (NRCMs) and H9c2 cells with adenovirus vector\u2010mediated overexpression of Flt3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our results demonstrated that following chronic Ang II infusion for 4\u00a0weeks, the mice exhibited heart hypertrophy, fibrosis, apoptosis and contractile dysfunction. Meanwhile, Ang II induced autophagic responses in mouse hearts, as evidenced by increased LC3 II and decreased P62 expression. These pathological alterations in Ang II\u2010treated mice were significantly ameliorated by Flt3 activation with FL administration. In NRCMs and Flt3\u2010overexpressed H9c2 cells, FL attenuated Ang II\u2010induced pathological autophagy and inactivated AMPK\/mTORC1\/FoxO3a signalling, thereby efficiently mitigating cell hypertrophy and apoptosis. Conversely, the AMPK activator metformin or the mTORC1 inhibitor rapamycin reversed the effects of FL on the alterations of autophagy, hypertrophy and apoptosis in cardiomyocytes induced by Ang II.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Flt3 activation ameliorates cardiac hypertrophy, fibrosis and contractile dysfunction in the mouse model of chronic pressure overload, most likely via suppressing AMPK\/mTORC1\/FoxO3a\u2010mediated autophagy. These results provide new evidence supporting Flt3 as a novel therapeutic target in maladaptive cardiac remodelling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.13519","type":"journal-article","created":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T17:16:03Z","timestamp":1591031763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Activated FMS\u2010like tyrosine kinase 3 ameliorates angiotensin II\u2010induced cardiac remodelling"],"prefix":"10.1111","volume":"230","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8670-0662","authenticated-orcid":false,"given":"Wenzhuo","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Sciences Xi'an Jiaotong University Health Science Center Xi\u2019an Shaanxi China"},{"name":"Key Laboratory of Environment and Genes Related to Diseases Ministry of Education Xi'an Jiaotong University Xi\u2019an 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