{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T08:25:40Z","timestamp":1768551940727,"version":"3.49.0"},"reference-count":15,"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":[[2012,9,28]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Heart failure (HF) is often the end phase of maladaptive cardiac hypertrophy. A contributing factor is activation of a hypertrophic gene expression program controlled by decreased class II histone deacetylase (HDAC) transcriptional repression via HDAC phosphorylation. Cardiac-specific overexpression of G proteinen\u2013coupled receptor kinase-5 (GRK5) has previously been shown to possess nuclear activity as a HDAC5 kinase, promoting an intolerance to in vivo ventricular pressure overload; however, its endogenous requirement in adaptive and maladaptive hypertrophy remains unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              We used mouse models with global or cardiomyocyte-specific\n              <jats:italic>GRK5<\/jats:italic>\n              gene deletion to determine the absolute requirement of endogenous GRK5 for cardiac hypertrophy and HF development after chronic hypertrophic stimuli.\n            <\/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              Mice with global deletion of\n              <jats:italic>GRK5<\/jats:italic>\n              were subjected to transverse aortic constriction. At 12 weeks, these mice showed attenuated hypertrophy, remodeling, and hypertrophic gene transcription along with preserved cardiac function. Global\n              <jats:italic>GRK5<\/jats:italic>\n              deletion also diminished hypertrophy and related gene expression due to chronic phenylephrine infusion. We then generated mice with conditional, cardiac-specific deletion of\n              <jats:italic>GRK5<\/jats:italic>\n              that also demonstrated similar protection from pathological cardiac hypertrophy and HF after transverse aortic constriction.\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 define myocyte GRK5 as a critical regulator of pathological cardiac growth after ventricular pressure overload, supporting its role as an endogenous (patho)-physiological HDAC kinase. Further, these results define GRK5 as a potential therapeutic target to limit HF development after hypertrophic stress.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.112.273367","type":"journal-article","created":{"date-parts":[[2012,8,3]],"date-time":"2012-08-03T04:25:27Z","timestamp":1343967927000},"page":"1048-1053","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":83,"title":["Determining the Absolute Requirement of G Protein\u2013Coupled Receptor Kinase 5 for Pathological Cardiac Hypertrophy"],"prefix":"10.1161","volume":"111","author":[{"given":"Jessica I.","family":"Gold","sequence":"first","affiliation":[{"name":"From the Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA (J.I.G., W.J.K.); Center for Translational Medicine (E.G., X.S., W.J.K.) and the Department of Pharmacology (W.J.K.), Temple University School of Medicine, Philadelphia, PA; and the Department of Medicine, Duke University Medical Center, Durham, NC (R.T.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA (J.I.G., W.J.K.); Center for Translational Medicine (E.G., X.S., W.J.K.) and the Department of Pharmacology (W.J.K.), Temple University School of Medicine, Philadelphia, PA; and the Department of Medicine, Duke University Medical Center, Durham, NC (R.T.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiying","family":"Shang","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA (J.I.G., W.J.K.); Center for Translational Medicine (E.G., X.S., W.J.K.) and the Department of Pharmacology (W.J.K.), Temple University School of Medicine, Philadelphia, PA; and the Department of Medicine, Duke University Medical Center, Durham, NC (R.T.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard T.","family":"Premont","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA (J.I.G., W.J.K.); Center for Translational Medicine (E.G., X.S., W.J.K.) and the Department of Pharmacology (W.J.K.), Temple University School of Medicine, Philadelphia, PA; and the Department of Medicine, Duke University Medical Center, Durham, NC (R.T.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter J.","family":"Koch","sequence":"additional","affiliation":[{"name":"From the Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA (J.I.G., W.J.K.); Center for Translational Medicine (E.G., X.S., W.J.K.) and the Department of Pharmacology (W.J.K.), Temple University School of Medicine, Philadelphia, PA; and the Department of Medicine, Duke University Medical Center, Durham, NC (R.T.P.)."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24178"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1983"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24144"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.19.8467-8476.2004"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27374"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803153105"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.19.8374-8385.2004"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)81048-X"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.105.608968"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.107.168336"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.03.015"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.246447"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31901"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1750"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.111.962563"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.112.273367","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:48:12Z","timestamp":1715572092000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.112.273367"}},"subtitle":["Short Communication"],"short-title":[],"issued":{"date-parts":[[2012,9,28]]},"references-count":15,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,9,28]]}},"alternative-id":["10.1161\/CIRCRESAHA.112.273367"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.112.273367","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,9,28]]},"assertion":[{"value":"2012-05-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-08-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-08-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}