{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T12:29:37Z","timestamp":1792499377337,"version":"4.5.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>In the failing heart, persistent \u03b2-adrenergic receptor activation is thought to induce myocyte death by protein kinase A (PKA)-dependent and PKA-independent activation of calcium\/calmodulin-dependent kinase II. \u03b2-adrenergic signaling pathways also are capable of activating cardioprotective mechanisms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>This study used a novel PKA inhibitor peptide to inhibit PKA activity to test the hypothesis that \u03b2-adrenergic receptor signaling causes cell death through PKA-dependent pathways and cardioprotection through PKA-independent pathways.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              In PKA inhibitor peptide transgenic mice, chronic isoproterenol failed to induce cardiac hypertrophy, fibrosis, and myocyte apoptosis, and decreased cardiac function. In cultured adult feline ventricular myocytes, PKA inhibition protected myocytes from death induced by \u03b21-adrenergic receptor agonists by preventing cytosolic and sarcoplasmic reticulum Ca\n              <jats:sup>2+<\/jats:sup>\n              overload and calcium\/calmodulin-dependent kinase II activation. PKA inhibition revealed a cardioprotective role of \u03b2-adrenergic signaling via cAMP\/exchange protein directly activated by cAMP\/Rap1\/Rac\/extracellular signal-regulated kinase pathway. Selective PKA inhibition causes protection in the heart after myocardial infarction that was superior to \u03b2-blocker therapy.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>These results suggest that selective block of PKA could be a novel heart failure therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.112.273896","type":"journal-article","created":{"date-parts":[[2012,10,27]],"date-time":"2012-10-27T01:11:26Z","timestamp":1351300286000},"page":"498-509","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":145,"title":["Cardiotoxic and Cardioprotective Features of Chronic \u03b2-Adrenergic Signaling"],"prefix":"10.1161","volume":"112","author":[{"given":"Xiaoying","family":"Zhang","sequence":"first","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (X.Z., C.S., M.T., J.J., C.M., X.A., Y.L., A.T., J.W., H.G., F.W., X.J.G., X.C.), Center for Translational Medicine and Department of Pharmacology (E.G.), and Department of Physiology (S.P.K.), Temple University School of Medicine, Philadelphia, PA; College of Biological Sciences, Shanghai Jiaotong University, Shanghai, China (X.A.); The Third Military Medical University, Chongqing, China (Y.L., L.Z., C.Z.); and Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Szeto","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (X.Z., C.S., M.T., J.J., C.M., X.A., Y.L., A.T., J.W., H.G., F.W., X.J.G., X.C.), Center for Translational Medicine and Department of Pharmacology (E.G.), and Department of Physiology (S.P.K.), Temple University School of Medicine, Philadelphia, PA; College of Biological Sciences, Shanghai Jiaotong University, Shanghai, China (X.A.); The Third Military Medical University, Chongqing, China (Y.L., L.Z., C.Z.); and Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (X.Z., C.S., M.T., J.J., C.M., X.A., Y.L., A.T., J.W., H.G., F.W., X.J.G., X.C.), Center for Translational Medicine and Department of Pharmacology (E.G.), and Department of Physiology (S.P.K.), Temple University School of Medicine, Philadelphia, PA; College of Biological Sciences, Shanghai Jiaotong University, Shanghai, China (X.A.); The Third Military Medical University, Chongqing, China (Y.L., L.Z., C.Z.); and Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxin","family":"Tang","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (X.Z., C.S., M.T., J.J., C.M., X.A., Y.L., A.T., J.W., H.G., F.W., X.J.G., X.C.), Center for Translational Medicine and Department of Pharmacology (E.G.), and Department of Physiology (S.P.K.), Temple University School of Medicine, Philadelphia, PA; College of Biological Sciences, Shanghai Jiaotong University, Shanghai, China (X.A.); The Third Military Medical University, Chongqing, China (Y.L., L.Z., C.Z.); and Department of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Jin","sequence":"additional","affiliation":[{"name":"From the Cardiovascular Research Center and Department of Physiology (X.Z., C.S., M.T., J.J., C.M., X.A., Y.L., A.T., J.W., H.G., F.W., X.J.G., X.C.), Center for Translational Medicine and Department of Pharmacology (E.G.), and Department of Physiology (S.P.K.), Temple University School of Medicine, Philadelphia, PA; 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