{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T07:09:21Z","timestamp":1793948961296,"version":"4.8.0"},"reference-count":24,"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":[[2015,4,10]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale<\/jats:underline>\n                      :\n                    <\/jats:title>\n                    <jats:p>Cyclic nucleotides are second messengers that regulate cardiomyocyte function through compartmentalized signaling in discrete subcellular microdomains. However, the role of different microdomains and their changes in cardiac disease are not well understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective<\/jats:underline>\n                      :\n                    <\/jats:title>\n                    <jats:p>To directly visualize alterations in \u03b2-adrenergic receptor\u2013associated cAMP and cGMP microdomain signaling in early cardiac disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results<\/jats:underline>\n                      :\n                    <\/jats:title>\n                    <jats:p>\n                      Unexpectedly, measurements of cell shortening revealed augmented \u03b2-adrenergic receptor\u2013stimulated cardiomyocyte contractility by atrial natriuretic peptide\/cGMP signaling in early cardiac hypertrophy after transverse aortic constriction, which was in sharp contrast to well-documented \u03b2-adrenergic and natriuretic peptide signaling desensitization during chronic disease. Real-time cAMP analysis in \u03b2\n                      <jats:sub>1<\/jats:sub>\n                      - and \u03b2\n                      <jats:sub>2<\/jats:sub>\n                      -adrenergic receptor\u2013associated membrane microdomains using a novel membrane-targeted F\u00f6rster resonance energy transfer\u2013based biosensor transgenically expressed in mice revealed that this unexpected atrial natriuretic peptide effect is brought about by spatial redistribution of cGMP-sensitive phosphodiesterases 2 and 3 between both receptor compartments. Functionally, this led to a significant shift in cGMP\/cAMP cross-talk and, in particular, to cGMP-driven augmentation of contractility in vitro and in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions<\/jats:underline>\n                      :\n                    <\/jats:title>\n                    <jats:p>Redistribution of cGMP-regulated phosphodiesterases and functional reorganization of receptor-associated microdomains occurs in early cardiac hypertrophy, affects cGMP-mediated contractility, and might represent a previously not recognized therapeutically relevant compensatory mechanism to sustain normal heart function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.116.306082","type":"journal-article","created":{"date-parts":[[2015,2,16]],"date-time":"2015-02-16T23:27:00Z","timestamp":1424129220000},"page":"1304-1311","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":102,"title":["Microdomain Switch of cGMP-Regulated Phosphodiesterases Leads to ANP-Induced Augmentation of \u03b2-Adrenoceptor-Stimulated Contractility in Early Cardiac Hypertrophy"],"prefix":"10.1161","volume":"116","author":[{"given":"Ruwan K.","family":"Perera","sequence":"first","affiliation":[{"name":"From the Emmy Noether Group of the DFG, European Heart Research Institute G\u00f6ttingen, G\u00f6ttingen, Germany (R.K.P., J.U.S., D.H., V.O.N.); Heart Research Center G\u00f6ttingen, Georg August University Medical Center, G\u00f6ttingen, Germany (R.K.P., J.U.S., J.H.S., D.H., S.E.L., A.E.-A., V.O.N.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.P, J.U.S., V.O.N.); German Center for Cardiovascular Research (DZHK; S.E.L., V.O.N.) and Instutite of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia U.","family":"Sprenger","sequence":"additional","affiliation":[{"name":"From the Emmy Noether Group of the DFG, European Heart Research Institute G\u00f6ttingen, G\u00f6ttingen, Germany (R.K.P., J.U.S., D.H., V.O.N.); Heart Research Center G\u00f6ttingen, Georg August University Medical Center, G\u00f6ttingen, Germany (R.K.P., J.U.S., J.H.S., D.H., S.E.L., A.E.-A., V.O.N.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.P, J.U.S., V.O.N.); German Center for Cardiovascular Research (DZHK; S.E.L., V.O.N.) and Instutite of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia H.","family":"Steinbrecher","sequence":"additional","affiliation":[{"name":"From the Emmy Noether Group of the DFG, European Heart Research Institute G\u00f6ttingen, G\u00f6ttingen, Germany (R.K.P., J.U.S., D.H., V.O.N.); Heart Research Center G\u00f6ttingen, Georg August University Medical Center, G\u00f6ttingen, Germany (R.K.P., J.U.S., J.H.S., D.H., S.E.L., A.E.-A., V.O.N.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.P, J.U.S., V.O.N.); German Center for Cardiovascular Research (DZHK; S.E.L., V.O.N.) and Instutite of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"H\u00fcbscher","sequence":"additional","affiliation":[{"name":"From the Emmy Noether Group of the DFG, European Heart Research Institute G\u00f6ttingen, G\u00f6ttingen, Germany (R.K.P., J.U.S., D.H., V.O.N.); Heart Research Center G\u00f6ttingen, Georg August University Medical Center, G\u00f6ttingen, Germany (R.K.P., J.U.S., J.H.S., D.H., S.E.L., A.E.-A., V.O.N.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.P, J.U.S., V.O.N.); German Center for Cardiovascular Research (DZHK; S.E.L., V.O.N.) and Instutite of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan E.","family":"Lehnart","sequence":"additional","affiliation":[{"name":"From the Emmy Noether Group of the DFG, European Heart Research Institute G\u00f6ttingen, G\u00f6ttingen, Germany (R.K.P., J.U.S., D.H., V.O.N.); Heart Research Center G\u00f6ttingen, Georg August University Medical Center, G\u00f6ttingen, Germany (R.K.P., J.U.S., J.H.S., D.H., S.E.L., A.E.-A., V.O.N.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.P, J.U.S., V.O.N.); German Center for Cardiovascular Research (DZHK; S.E.L., V.O.N.) and Instutite of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Abesser","sequence":"additional","affiliation":[{"name":"From the Emmy Noether Group of the DFG, European Heart Research Institute G\u00f6ttingen, G\u00f6ttingen, Germany (R.K.P., J.U.S., D.H., V.O.N.); Heart Research Center G\u00f6ttingen, Georg August University Medical Center, G\u00f6ttingen, Germany (R.K.P., J.U.S., J.H.S., D.H., S.E.L., A.E.-A., V.O.N.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.P, J.U.S., V.O.N.); German Center for Cardiovascular Research (DZHK; S.E.L., V.O.N.) and Instutite of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Schuh","sequence":"additional","affiliation":[{"name":"From the Emmy Noether Group of the DFG, European Heart Research Institute G\u00f6ttingen, G\u00f6ttingen, Germany (R.K.P., J.U.S., D.H., V.O.N.); Heart Research Center G\u00f6ttingen, Georg August University Medical Center, G\u00f6ttingen, Germany (R.K.P., J.U.S., J.H.S., D.H., S.E.L., A.E.-A., V.O.N.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.P, J.U.S., V.O.N.); German Center for Cardiovascular Research (DZHK; S.E.L., V.O.N.) and Instutite of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"El-Armouche","sequence":"additional","affiliation":[{"name":"From the Emmy Noether Group of the DFG, European Heart Research Institute G\u00f6ttingen, G\u00f6ttingen, Germany (R.K.P., J.U.S., D.H., V.O.N.); Heart Research Center G\u00f6ttingen, Georg August University Medical Center, G\u00f6ttingen, Germany (R.K.P., J.U.S., J.H.S., D.H., S.E.L., A.E.-A., V.O.N.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.P, J.U.S., V.O.N.); German Center for Cardiovascular Research (DZHK; S.E.L., V.O.N.) and Instutite of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viacheslav O.","family":"Nikolaev","sequence":"additional","affiliation":[{"name":"From the Emmy Noether Group of the DFG, European Heart Research Institute G\u00f6ttingen, G\u00f6ttingen, Germany (R.K.P., J.U.S., D.H., V.O.N.); Heart Research Center G\u00f6ttingen, Georg August University Medical Center, G\u00f6ttingen, Germany (R.K.P., J.U.S., J.H.S., D.H., S.E.L., A.E.-A., V.O.N.); Institute of Experimental Cardiovascular Research, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (R.K.P, J.U.S., V.O.N.); German Center for Cardiovascular Research (DZHK; S.E.L., V.O.N.) and Instutite of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.262899"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12077"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.106.144501"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.230698"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2001.104.re15"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1185988"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.02.009"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI17061"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11273"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198207223070401"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000094745.28948.4D"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.198"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302437"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.643536"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000102042.83024.CA"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.278.1.H33"},{"key":"e_1_3_5_18_2","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S0022-3565(24)35143-2","article-title":"Effects of atrial natriuretic peptide on left ventricular performance in conscious dogs before and after pacing-induced heart failure.","volume":"291","author":"Ohte N","year":"1999","unstructured":"Ohte N, Cheng CP, Suzuki M, Little WC. Effects of atrial natriuretic peptide on left ventricular performance in conscious dogs before and after pacing-induced heart failure. J Pharmacol Exp Ther. 1999;291:589\u2013595.","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.197947"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000165128.39715.87"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.599241"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.05.057"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601968"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.03.016"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001734200"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.116.306082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T03:36:45Z","timestamp":1747625805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.116.306082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,10]]},"references-count":24,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,4,10]]}},"alternative-id":["10.1161\/CIRCRESAHA.116.306082"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.116.306082","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.725357765.793506947","asserted-by":"object"}]},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,10]]},"assertion":[{"value":"2015-01-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}