{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:32:02Z","timestamp":1791235922095,"version":"4.1.0"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2000,2,22]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>\u2014Senescent hearts are characterized by diastolic dysfunction and a decrease in sarcoplasmic reticulum (SR) Ca<jats:sup>2+<\/jats:sup>-ATPase protein (SERCA2a).<\/jats:p><jats:p><jats:italic>Methods and Results<\/jats:italic>\u2014To test the hypothesis that an increase in SERCA2a could improve cardiac function in senescent rats (age 26 months), we used a catheter-based technique of adenoviral gene transfer to achieve global myocardial transduction of SERCA2a in vivo. Adult rat hearts aged 6 months and senescent rat hearts infected with an adenovirus containing the reporter gene \u03b2-galactosidase were used as controls. Two days after infection, parameters of systolic and diastolic function were measured in open-chest rats. Cardiac SERCA2a protein and ATPase activity were significantly decreased in senescent hearts compared with adult rats (\u0394 \u221230\u00b14% and \u221249\u00b15%) and were restored to adult levels after infection with Ad.SERCA2a. At baseline, left ventricular systolic pressure and +dP\/dt were unaltered in senescent hearts; however, diastolic parameters were adversely affected with an increase in the left ventricular time constant of isovolumic relaxation and diastolic pressure (\u0394 +29\u00b19% and +38\u00b112%) and a decrease in \u2212dP\/dt (\u0394 \u221226\u00b111%). Overexpression of SERCA2a did not significantly affect left ventricular systolic pressure but did increase +dP\/dt (\u0394 +28\u00b110%) in the senescent heart. Overexpression of SERCA2a restored the left ventricular time constant of isovolumic relaxation and \u2212dP\/dt to adult levels. Infection of senescent hearts with Ad.SERCA2a markedly improved rate-dependent contractility and diastolic function in senescent hearts.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic>\u2014These results support the hypothesis that decreased Ca<jats:sup>2+<\/jats:sup>-ATPase activity contributes to the functional abnormalities observed in senescent hearts and demonstrates that Ca<jats:sup>2+<\/jats:sup>cycling proteins can be targeted in the senescent heart to improve cardiac function.<\/jats:p>","DOI":"10.1161\/01.cir.101.7.790","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"790-796","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":195,"title":["Restoration of Diastolic Function in Senescent Rat Hearts Through Adenoviral Gene Transfer of Sarcoplasmic Reticulum Ca<sup>2+<\/sup>-ATPase"],"prefix":"10.1161","volume":"101","author":[{"given":"Ulrich","family":"Schmidt","sequence":"first","affiliation":[{"name":"From the Cardiovascular Research Center and the Cardiology Division (F.d.M., M.I.M., T.M., A.R., R.J.H.) and Anesthesia Department (U.S.), Harvard Medical School and Massachusetts General Hospital; and Boston University School of Medicine (J.K.G.), Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"del Monte","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and the Cardiology Division (F.d.M., M.I.M., T.M., A.R., R.J.H.) and Anesthesia Department (U.S.), Harvard Medical School and Massachusetts General Hospital; and Boston University School of Medicine (J.K.G.), Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael I.","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and the Cardiology Division (F.d.M., M.I.M., T.M., A.R., R.J.H.) and Anesthesia Department (U.S.), Harvard Medical School and Massachusetts General Hospital; and Boston University School of Medicine (J.K.G.), Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Matsui","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and the Cardiology Division (F.d.M., M.I.M., T.M., A.R., R.J.H.) and Anesthesia Department (U.S.), Harvard Medical School and Massachusetts General Hospital; and Boston University School of Medicine (J.K.G.), Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith K.","family":"Gwathmey","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and the Cardiology Division (F.d.M., M.I.M., T.M., A.R., R.J.H.) and Anesthesia Department (U.S.), Harvard Medical School and Massachusetts General Hospital; and Boston University School of Medicine (J.K.G.), Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and the Cardiology Division (F.d.M., M.I.M., T.M., A.R., R.J.H.) and Anesthesia Department (U.S.), Harvard Medical School and Massachusetts General Hospital; and Boston University School of Medicine (J.K.G.), Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J.","family":"Hajjar","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and the Cardiology Division (F.d.M., M.I.M., T.M., A.R., R.J.H.) and Anesthesia Department (U.S.), Harvard Medical School and Massachusetts General Hospital; and Boston University School of Medicine (J.K.G.), Boston, Mass."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1997.tb01468.x"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-9032-3_6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198011133032009"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(97)00359-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1993.73.2.413"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1996.81.4.1488"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jmicro.a023504"},{"key":"e_1_3_2_8_2","first-page":"H68","volume":"271","year":"1996","unstructured":"Tate CA, Helgason T, Hyek MF, McBride RP, Chen M, Richardson MA, Taffet GE. 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