{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:22:07Z","timestamp":1791336127455,"version":"4.3.1"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2009,10,9]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Rationale<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Multiple cyclic nucleotide phosphodiesterases (PDEs) degrade cAMP in cardiomyocytes but the role of PDEs in controlling cAMP signaling during pathological cardiac hypertrophy is poorly defined.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Objective<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Evaluate the \u03b2-adrenergic regulation of cardiac contractility and characterize the changes in cardiomyocyte cAMP signals and cAMP-PDE expression and activity following cardiac hypertrophy.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Methods and Results<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            Cardiac hypertrophy was induced in rats by thoracic aortic banding over a time period of 5 weeks and was confirmed by anatomic measurements and echocardiography. Ex vivo myocardial function was evaluated in Langendorff-perfused hearts. Engineered cyclic nucleotide-gated (CNG) channels were expressed in single cardiomyocytes to monitor subsarcolemmal cAMP using whole-cell patch-clamp recordings of the associated CNG current (\n            <jats:italic>I<\/jats:italic>\n            <jats:sub>CNG<\/jats:sub>\n            ). PDE variant activity and protein level were determined in purified cardiomyocytes. Aortic stenosis rats exhibited a 67% increase in heart weight compared to sham-operated animals. The inotropic response to maximal \u03b2-adrenergic stimulation was reduced by \u224854% in isolated hypertrophied hearts, along with a \u224832% decrease in subsarcolemmal cAMP levels in hypertrophied myocytes. Total cAMP hydrolytic activity as well as PDE3 and PDE4 activities were reduced in hypertrophied myocytes, because of a reduction of PDE3A, PDE4A, and PDE4B, whereas PDE4D was unchanged. Regulation of \u03b2-adrenergic cAMP signals by PDEs was blunted in hypertrophied myocytes, as demonstrated by the diminished effects of IBMX (100 \u03bcmol\/L) and of both the PDE3 inhibitor cilostamide (1 \u03bcmol\/L) and the PDE4 inhibitor Ro 201724 (10 \u03bcmol\/L).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>\n                <jats:underline>Conclusions<\/jats:underline>\n                :\n              <\/jats:italic>\n            <\/jats:bold>\n            \u03b2-Adrenergic desensitization is accompanied by a reduction in cAMP-PDE and an altered modulation of \u03b2-adrenergic cAMP signals in cardiac hypertrophy.\n          <\/jats:p>","DOI":"10.1161\/circresaha.109.197947","type":"journal-article","created":{"date-parts":[[2009,9,11]],"date-time":"2009-09-11T01:44:56Z","timestamp":1252633496000},"page":"784-792","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":127,"title":["Decreased Expression and Activity of cAMP Phosphodiesterases in Cardiac Hypertrophy and Its Impact on \u03b2-Adrenergic cAMP Signals"],"prefix":"10.1161","volume":"105","author":[{"given":"Aniella","family":"Abi-Gerges","sequence":"first","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; Universite\u0301 Paris 7 (C.H., J.-L.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wito","family":"Richter","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; Universite\u0301 Paris 7 (C.H., J.-L.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Lefebvre","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; Universite\u0301 Paris 7 (C.H., J.-L.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Mateo","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; Universite\u0301 Paris 7 (C.H., J.-L.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Varin","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; Universite\u0301 Paris 7 (C.H., J.-L.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Heymes","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; Universite\u0301 Paris 7 (C.H., J.-L.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane-Lise","family":"Samuel","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; Universite\u0301 Paris 7 (C.H., J.-L.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Lugnier","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; Universite\u0301 Paris 7 (C.H., J.-L.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Conti","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; Universite\u0301 Paris 7 (C.H., J.-L.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodolphe","family":"Fischmeister","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; Universite\u0301 Paris 7 (C.H., J.-L.S.)..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gre\u0301goire","family":"Vandecasteele","sequence":"additional","affiliation":[{"name":"From the Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 769 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Universite\u0301 Paris-Sud 11, IFR141 (A.A.-G., F.L., P.M., A.V., R.F., G.V.), Cha\u0302tenay-Malabry, France; Department of Obstetrics, Gynecology, and Reproductive Sciences (W.R., M.C.), University of California, San Francisco; Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale UMR-S 689 (C.H., J.-L.S.), Paris, France; 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