{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T02:51:49Z","timestamp":1789095109649,"version":"build-2803163510"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2021,10,12]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Inflammation contributes to the pathogenesis of heart failure, but there is limited understanding of inflammation\u2019s potential benefits. Inflammatory cells secrete MYDGF (myeloid-derived growth factor) to promote tissue repair after acute myocardial infarction. We hypothesized that MYDGF has a role in cardiac adaptation to persistent pressure overload.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              We defined the cellular sources and function of MYDGF in wild-type (WT),\n              <jats:italic>Mydgf<\/jats:italic>\n              -deficient (\n              <jats:italic>Mydgf<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ), and\n              <jats:italic>Mydgf<\/jats:italic>\n              bone marrow\u2013chimeric or bone marrow\u2013conditional transgenic mice with pressure overload\u2013induced heart failure after transverse aortic constriction surgery. We measured MYDGF plasma concentrations by targeted liquid chromatography\u2013mass spectrometry. We identified MYDGF signaling targets by phosphoproteomics and substrate-based kinase activity inference. We recorded Ca\n              <jats:sup>2+<\/jats:sup>\n              transients and sarcomere contractions in isolated cardiomyocytes. Additionally, we explored the therapeutic potential of recombinant MYDGF.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              MYDGF protein abundance increased in the left ventricular myocardium and in blood plasma of pressure-overloaded mice. Patients with severe aortic stenosis also had elevated MYDGF plasma concentrations, which declined after transcatheter aortic valve implantation. Monocytes and macrophages emerged as the main MYDGF sources in the pressure-overloaded murine heart. While\n              <jats:italic>Mydgf<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice had no apparent phenotype at baseline, they developed more severe left ventricular hypertrophy and contractile dysfunction during pressure overload than WT mice. Conversely, conditional transgenic overexpression of MYDGF in bone marrow\u2013derived inflammatory cells attenuated pressure overload\u2013induced hypertrophy and dysfunction. Mechanistically, MYDGF inhibited G protein\u2013coupled receptor agonist\u2013induced hypertrophy and augmented SERCA2a (sarco\/endoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              -ATPase 2a) expression in cultured neonatal rat ventricular cardiomyocytes by enhancing PIM1 (Pim-1 proto-oncogene, serine\/threonine kinase) expression and activity. Along this line, cardiomyocytes from pressure-overloaded\n              <jats:italic>Mydgf<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice displayed reduced PIM1 and SERCA2a expression, greater hypertrophy, and impaired Ca\n              <jats:sup>2+<\/jats:sup>\n              cycling and sarcomere function compared with cardiomyocytes from pressure-overloaded WT mice. Transplanting\n              <jats:italic>Mydgf<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice with WT bone marrow cells augmented cardiac PIM1 and SERCA2a levels and ameliorated pressure overload\u2013induced hypertrophy and dysfunction. Pressure-overloaded\n              <jats:italic>Mydgf<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice were similarly rescued by adenoviral\n              <jats:italic>Serca2a<\/jats:italic>\n              gene transfer. Treating pressure-overloaded WT mice subcutaneously with recombinant MYDGF enhanced SERCA2a expression, attenuated left ventricular hypertrophy and dysfunction, and improved survival.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>These findings establish a MYDGF-based adaptive crosstalk between inflammatory cells and cardiomyocytes that protects against pressure overload\u2013induced heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.120.053365","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T09:00:17Z","timestamp":1628586017000},"page":"1227-1240","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":71,"title":["Myeloid-Derived Growth Factor Protects Against Pressure Overload\u2013Induced Heart Failure by Preserving Sarco\/Endoplasmic Reticulum Ca\n            <sup>2+<\/sup>\n            -ATPase Expression in Cardiomyocytes"],"prefix":"10.1161","volume":"144","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4388-2117","authenticated-orcid":true,"given":"Mortimer","family":"Korf-Klingebiel","sequence":"first","affiliation":[{"name":"Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology (M.K.-K., M.R.R., F.P., F.J., X.W., Y.W., K.C.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4135-8434","authenticated-orcid":true,"given":"Marc R.","family":"Reboll","sequence":"additional","affiliation":[{"name":"Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology (M.K.-K., M.R.R., F.P., F.J., X.W., Y.W., K.C.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1076-5272","authenticated-orcid":true,"given":"Felix","family":"Polten","sequence":"additional","affiliation":[{"name":"Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology (M.K.-K., M.R.R., F.P., F.J., X.W., Y.W., K.C.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute for Molecular and Cellular Physiology (N.W., T.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8817-8118","authenticated-orcid":true,"given":"Felix","family":"J\u00e4ckle","sequence":"additional","affiliation":[{"name":"Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology (M.K.-K., M.R.R., F.P., F.J., X.W., Y.W., K.C.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5429-3126","authenticated-orcid":true,"given":"Xuekun","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology (M.K.-K., M.R.R., F.P., F.J., X.W., Y.W., K.C.W.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9318-3368","authenticated-orcid":true,"given":"Marinos","family":"Kallikourdis","sequence":"additional","affiliation":[{"name":"Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy (M.K., P.K., G.C.)."},{"name":"Humanitas University, Pieve Emanuele, Milan, Italy (M.K., G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Kunderfranco","sequence":"additional","affiliation":[{"name":"Humanitas Clinical and Research Center IRCCS, Rozzano, Milan, Italy (M.K., P.K., 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