{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:45:14Z","timestamp":1792514714817,"version":"4.5.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,10,4]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Structural and electrophysiological remodeling characterize heart failure (HF) enhancing arrhythmias. PKD1 (protein kinase D1) is upregulated in HF and mediates pathological hypertrophic signaling, but its role in K+ channel remodeling and arrhythmogenesis in HF is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">We performed echocardiography, electrophysiology, and expression analysis in wild\u2010type and PKD1 cardiomyocyte\u2010specific knockout (cKO) mice following transverse aortic constriction (TAC). PKD1\u2010cKO mice exhibited significantly less cardiac hypertrophy post\u2010TAC and were protected from early decline in cardiac contractile function (3\u2009weeks post\u2010TAC) but not the progression to HF at 7\u2009weeks post\u2010TAC. Wild\u2010type mice exhibited ventricular action potential duration prolongation at 8\u2009weeks post\u2010TAC, which was attenuated in PKD1\u2010cKO, consistent with larger K+ currents via the transient outward current, sustained current, inward rectifier K+ current, and rapid delayed rectifier K+ current and increased expression of corresponding K+ channels. Conversely, reduction of slowly inactivating K+ current was independent of PKD1 in HF. Acute PKD inhibition slightly increased transient outward current in TAC and sham wild\u2010type myocytes but did not alter other K+ currents. Sham PKD1\u2010cKO versus wild\u2010type also exhibited larger transient outward current and faster early action potential repolarization. Tachypacing\u2010induced action potential duration alternans in TAC animals was increased and independent of PKD1, but diastolic arrhythmogenic activities were reduced in PKD1\u2010cKO.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our data indicate an important role for PKD1 in the HF\u2010related hypertrophic response and K+ channel downregulation. Therefore, PKD1 inhibition may represent a therapeutic strategy to reduce hypertrophy and arrhythmias; however, PKD1 inhibition may not prevent disease progression and reduced contractility in HF.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027573","type":"journal-article","created":{"date-parts":[[2022,9,29]],"date-time":"2022-09-29T09:45:29Z","timestamp":1664444729000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Protein Kinase D1 Regulates Cardiac Hypertrophy, Potassium Channel Remodeling, and Arrhythmias in Heart Failure"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8874-4765","authenticated-orcid":false,"given":"Julie","family":"Bossuyt","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of California Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-0852","authenticated-orcid":false,"given":"Johanna M.","family":"Borst","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Verberckmoes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7811-7362","authenticated-orcid":false,"given":"Logan R. J.","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2237-9483","authenticated-orcid":false,"given":"Donald M.","family":"Bers","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3113-221X","authenticated-orcid":false,"given":"Bence","family":"Hegyi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.246447"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.107.168211"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00009"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1124\/molpharm.121.000341"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.169755"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2008.08.030"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712265105"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.047"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00240"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.10.3875-3888.2006"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.11.036"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.24.2863"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.030730"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.316947"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1690"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.6.623"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000120390.68287.BB"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.013894"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(87)90305-5"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00017-6"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.73.2.379"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00274-5"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.170050"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCEP.117.005852"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.03.007"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2013.10.010"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38022"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-020-00834-8"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/509282a"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.063347"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.09.012"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.318402"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2004.063446"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-09-1145"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813013106"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.006185"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm100075z"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm100076w"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202100110"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00256-3"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.85.11.1067"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-021-00850-2"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2020.05.018"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4489"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2019.01.001"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/circep.108.842799"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020911-153308"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000194329.41863.89"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000125626.33738.E2"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.982298"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1159\/000491007"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709851200"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.2.285"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00228-8"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00002.2005"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abg0927"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718211115"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab006"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1581-4"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01893"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-021-00900-9"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.223586"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP275418"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.122.027573","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T12:25:05Z","timestamp":1715603105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.122.027573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,4]]},"references-count":63,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2022,10,4]]}},"alternative-id":["10.1161\/JAHA.122.027573"],"URL":"https:\/\/doi.org\/10.1161\/jaha.122.027573","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,4]]},"assertion":[{"value":"2022-07-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e027573"}}