{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:55:28Z","timestamp":1792115728718,"version":"4.4.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2007,8,17]]},"abstract":"<jats:p>\n            Apelin constitutes a novel endogenous peptide system suggested to be involved in a broad range of physiological functions, including cardiovascular function, heart development, control of fluid homeostasis, and obesity. Apelin is also a catalytic substrate for angiotensin-converting enzyme 2, the key severe acute respiratory syndrome receptor. The in vivo physiological role of Apelin is still elusive. Here we report the generation of Apelin gene\u2013targeted mice. Apelin mutant mice are viable and fertile, appear healthy, and exhibit normal body weight, water and food intake, heart rates, and heart morphology. Intriguingly, aged Apelin knockout mice developed progressive impairment of cardiac contractility associated with systolic dysfunction in the absence of histological abnormalities. We also report that pressure overload induces upregulation of Apelin expression in the heart. Importantly, in pressure overload\u2013induced heart failure, loss of Apelin did not significantly affect the hypertrophy response, but Apelin mutant mice developed progressive heart failure. Global gene expression arrays and hierarchical clustering of differentially expressed genes in hearts of banded Apelin\n            <jats:sup>\u2212\/y<\/jats:sup>\n            and Apelin\n            <jats:sup>+\/y<\/jats:sup>\n            mice showed concerted upregulation of genes involved in extracellular matrix remodeling and muscle contraction. These genetic data show that the endogenous peptide Apelin is crucial to maintain cardiac contractility in pressure overload and aging.\n          <\/jats:p>","DOI":"10.1161\/circresaha.107.158659","type":"journal-article","created":{"date-parts":[[2007,8,3]],"date-time":"2007-08-03T01:18:17Z","timestamp":1186103897000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":280,"title":["Impaired Heart Contractility in Apelin Gene\u2013Deficient Mice Associated With Aging and Pressure Overload"],"prefix":"10.1161","volume":"101","author":[{"given":"Keiji","family":"Kuba","sequence":"first","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyong","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Imai","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Arab","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manyin","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Maekawa","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Leschnik","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Leibbrandt","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mato","family":"Markovic","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Schwaighofer","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Beetz","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Musialek","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Greg","family":"Neely","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vukoslav","family":"Komnenovic","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Kolm","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Metzler","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romeo","family":"Ricci","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromitsu","family":"Hara","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arabella","family":"Meixner","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Nghiem","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fayez","family":"Dawood","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kit Man","family":"Wong","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Sarao","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Cukerman","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinori","family":"Kimura","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz","family":"Hein","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Thalhammer","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter P.","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; Medical Top Track Program (K.K.) and Department of Molecular Pathogenesis (A.K.), Medical Research Institute, Tokyo Medical and Dental University, Japan; Heart and Stroke\/Richard Lewar Centre of Excellence and Toronto General Research Institute (L.Z., S.A., M.C., Y.M., M.N., X.C., F.D., K.M.W., R.S., E.C., P.P.L.), University Health Network, Ontario,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef M.","family":"Penninger","sequence":"additional","affiliation":[{"name":"From the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (K.K., Y.I., A.L., G.G.N., V.K., H.H., A.M., R.S., J.M.P.), Vienna; 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