{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:57:17Z","timestamp":1791489437458,"version":"4.3.4"},"reference-count":77,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2024,7,5]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Chronically elevated neurohumoral drive, and particularly elevated adrenergic tone leading to \u03b2-adrenergic receptor (\u03b2-AR) overstimulation in cardiac myocytes, is a key mechanism involved in the progression of heart failure. \u03b21-AR (\u03b21-adrenergic receptor) and \u03b22-ARs (\u03b22-adrenergic receptor) are the 2 major subtypes of \u03b2-ARs present in the human heart; however, they elicit different or even opposite effects on cardiac function and hypertrophy. For example, chronic activation of \u03b21-ARs drives detrimental cardiac remodeling while \u03b22-AR signaling is protective. The underlying molecular mechanisms for cardiac protection through \u03b22-ARs remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\u03b22-AR signaling mechanisms were studied in isolated neonatal rat ventricular myocytes and adult mouse ventricular myocytes using live cell imaging and Western blotting methods. Isolated myocytes and mice were used to examine the roles of \u03b22-AR signaling mechanisms in the regulation of cardiac hypertrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Here, we show that \u03b22-AR activation protects against hypertrophy through inhibition of phospholipaseC\u03b5 signaling at the Golgi apparatus. The mechanism for \u03b22-AR\u2013mediated phospholipase C inhibition requires internalization of \u03b22-AR, activation of Gi and G\u03b2\u03b3 subunit signaling at endosome and ERK (extracellular regulated kinase) activation. This pathway inhibits both angiotensin II and Golgi-\u03b21-AR\u2013mediated stimulation of phosphoinositide hydrolysis at the Golgi apparatus ultimately resulting in decreased PKD (protein kinase D) and histone deacetylase 5 phosphorylation and protection against cardiac hypertrophy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>This reveals a mechanism for \u03b22-AR antagonism of the phospholipase C\u03b5 pathway that may contribute to the known protective effects of \u03b22-AR signaling on the development of heart failure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.123.323201","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T05:04:10Z","timestamp":1717045450000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Internalized \u03b22-Adrenergic Receptors Oppose PLC-Dependent Hypertrophic Signaling"],"prefix":"10.1161","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5822-6342","authenticated-orcid":true,"given":"Wenhui","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3099-8812","authenticated-orcid":true,"given":"Alan V.","family":"Smrcka","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.101.5.558"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/415206a"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.22.7920"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2011.201"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.2000.1123"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.12.7059"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8160017"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6400"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000020220.79105.fd"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.01954.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0707622"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00453.2010"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-133983"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2016.02.015"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E14-10-1476"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806994200"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608495200"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.047"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.01.009"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183750"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1846707"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20031370"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.4.743"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100574200"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306904200"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.48167"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.231993"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.896357"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.06.002"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.170142"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.176024"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.317452"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.03.015"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2010.08.007"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2389"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1665"},{"key":"e_1_3_3_38_2","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0026-895X(24)12621-1","article-title":"\u03b2-adrenergic receptor subtype-specific signaling in cardiac myocytes from \u03b2(1) and \u03b2(2) adrenoceptor knockout mice.","volume":"60","author":"Devic E","year":"2001","unstructured":"Devic, E, Xiang, Y, Gould, D, Kobilka, B. \u03b2-adrenergic receptor subtype-specific signaling in cardiac myocytes from \u03b2(1) and \u03b2(2) adrenoceptor knockout mice. Mol Pharmacol. 2001;60:577\u2013583. PMID: 11502890","journal-title":"Mol Pharmacol"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204136200"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1831718100"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci110208"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.84.1.43"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1120378"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.107.041780"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1606267113"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.13.9572"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804745105"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.02.009"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05343-3"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.114.096800"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0158OC"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/28771"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608086200"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.65.092101.142243"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1994.1017"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113569"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1893"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2018.05.068"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0610906104"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.231514"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.35.24858"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-0255-7"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.11.009"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405878200"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210407"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3024"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804246105"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712265105"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2017.05.008"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.87.12.1172"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1042\/CBI20110162"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13800-7"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707936104"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.135335"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.09.019"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.39.24048"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.137.7.1525"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0077843"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.123.323201","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T16:05:50Z","timestamp":1748534750000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.123.323201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,5]]},"references-count":77,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,7,5]]}},"alternative-id":["10.1161\/CIRCRESAHA.123.323201"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.123.323201","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.06.07.544153","asserted-by":"object"}]},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,5]]},"assertion":[{"value":"2023-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-12","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}