{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:39:10Z","timestamp":1790987950711,"version":"4.1.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2007,5,15]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    The incidence of heart failure is ever-growing, and it is urgent to develop improved treatments. An attractive approach is gene therapy; however, the clinical barrier has yet to be broken because of several issues, including the lack of an ideal vector supporting safe and long-term myocardial transgene expression.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Here, we show that the use of a recombinant adeno-associated viral (rAAV6) vector containing a novel cardiac-selective enhancer\/promoter element can direct stable cardiac expression of a therapeutic transgene, the calcium (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    )-sensing S100A1, in a rat model of heart failure. The chronic heart failure\u2013rescuing properties of myocardial S100A1 expression, the result of improved sarcoplasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    handling, included improved contractile function and left ventricular remodeling. Adding to the clinical relevance, long-term S100A1 therapy had unique and additive beneficial effects over \u03b2-adrenergic receptor blockade, a current pharmacological heart failure treatment.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    These findings demonstrate that stable increased expression of S100A1 in the failing heart can be used for long-term reversal of LV dysfunction and remodeling. Thus, long-term, cardiac-targeted rAAV6-S100A1 gene therapy may be of potential clinical utility in human heart failure.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.106.671701","type":"journal-article","created":{"date-parts":[[2007,4,30]],"date-time":"2007-04-30T21:18:44Z","timestamp":1177967924000},"page":"2506-2515","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":158,"title":["Stable Myocardial-Specific AAV6-S100A1 Gene Therapy Results in Chronic Functional Heart Failure Rescue"],"prefix":"10.1161","volume":"115","author":[{"given":"Sven T.","family":"Pleger","sequence":"first","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., J.K.C., W.P., E.G., G.R., W.J.K.), Eugene Feiner Laboratory of Vascular Biology and Thrombosis (A.D.E.), and Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics (A.D.), Thomas Jefferson University, Philadelphia, Pa, and the Medizinische Universita\u0308tsklinik und..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Most","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., J.K.C., W.P., E.G., G.R., W.J.K.), Eugene Feiner Laboratory of Vascular Biology and Thrombosis (A.D.E.), and Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics (A.D.), Thomas Jefferson University, Philadelphia, Pa, and the Medizinische Universita\u0308tsklinik und..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Boucher","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., J.K.C., W.P., E.G., G.R., W.J.K.), Eugene Feiner Laboratory of Vascular Biology and Thrombosis (A.D.E.), and Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics (A.D.), Thomas Jefferson University, Philadelphia, Pa, and the Medizinische Universita\u0308tsklinik und..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Soltys","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., J.K.C., W.P., E.G., G.R., W.J.K.), Eugene Feiner Laboratory of Vascular Biology and Thrombosis (A.D.E.), and Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics (A.D.), Thomas Jefferson University, Philadelphia, Pa, and the Medizinische Universita\u0308tsklinik und..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Kurt","family":"Chuprun","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., J.K.C., W.P., E.G., G.R., W.J.K.), Eugene Feiner Laboratory of Vascular Biology and Thrombosis (A.D.E.), and Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics (A.D.), Thomas Jefferson University, Philadelphia, Pa, and the Medizinische Universita\u0308tsklinik und..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Pleger","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., J.K.C., W.P., E.G., G.R., W.J.K.), Eugene Feiner Laboratory of Vascular Biology and Thrombosis (A.D.E.), and Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics (A.D.), Thomas Jefferson University, Philadelphia, Pa, and the Medizinische Universita\u0308tsklinik und..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., J.K.C., W.P., E.G., G.R., W.J.K.), Eugene Feiner Laboratory of Vascular Biology and Thrombosis (A.D.E.), and Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics (A.D.), Thomas Jefferson University, Philadelphia, Pa, and the Medizinische Universita\u0308tsklinik und..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhijit","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., J.K.C., W.P., E.G., G.R., W.J.K.), Eugene Feiner Laboratory of Vascular Biology and Thrombosis (A.D.E.), and Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics (A.D.), Thomas Jefferson University, Philadelphia, Pa, and the Medizinische Universita\u0308tsklinik und..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Rengo","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., 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und..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo A.","family":"Katus","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., J.K.C., W.P., E.G., G.R., W.J.K.), Eugene Feiner Laboratory of Vascular Biology and Thrombosis (A.D.E.), and Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics (A.D.), Thomas Jefferson University, Philadelphia, Pa, and the Medizinische Universita\u0308tsklinik und..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea D.","family":"Eckhart","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine (S.T.P., P.M., M.B., S.S., J.K.C., W.P., E.G., G.R., A.D.E., J.E.R., W.J.K.), George Zallie and Family Laboratory of Cardiovascular Gene Therapy (S.T.P., M.B., 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