{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T19:43:32Z","timestamp":1787687012030,"version":"build-2784847793"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T00:00:00Z","timestamp":1607212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81922005"],"award-info":[{"award-number":["81922005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81930008"],"award-info":[{"award-number":["81930008"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81970306"],"award-info":[{"award-number":["81970306"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Key Research & Development Program of China","award":["2018YFC1312700"],"award-info":[{"award-number":["2018YFC1312700"]}]},{"name":"National Key Research & Development Program of China","award":["2018YFA0107403"],"award-info":[{"award-number":["2018YFA0107403"]}]},{"name":"Program of Innovative Research Team"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["81721001"],"award-info":[{"award-number":["81721001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018621","name":"Program for Changjiang Scholars and Innovative Research Team in University","doi-asserted-by":"publisher","award":["IRT1216"],"award-info":[{"award-number":["IRT1216"]}],"id":[{"id":"10.13039\/501100018621","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK039308"],"award-info":[{"award-number":["R01DK039308"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL119652"],"award-info":[{"award-number":["R01HL119652"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01HL74940"],"award-info":[{"award-number":["P01HL74940"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>G protein-coupled receptor kinase 4 (GRK4) has been reported to play an important role in hypertension, but little is known about its role in cardiomyocytes and myocardial infarction (MI). The goal of present study is to explore the role of GRK4 in the pathogenesis and progression of MI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We studied the expression and distribution pattern of GRK4 in mouse heart after MI. GRK4 A486V transgenic mice, inducible cardiomyocyte-specific GRK4 knockout mice, were generated and subjected to MI with their control mice. Cardiac infarction, cardiac function, cardiomyocyte apoptosis, autophagic activity, and HDAC4 phosphorylation were assessed. The mRNA and protein levels of GRK4 in the heart were increased after MI. Transgenic mice with the overexpression of human GRK4 wild type (WT) or human GRK4 A486V variant had increased cardiac infarction, exaggerated cardiac dysfunction and remodelling. In contrast, the MI-induced cardiac dysfunction and remodelling were ameliorated in cardiomyocyte-specific GRK4 knockout mice. GRK4 overexpression in cardiomyocytes aggravated apoptosis, repressed autophagy, and decreased beclin-1 expression, which were partially rescued by the autophagy agonist rapamycin. MI also induced the nuclear translocation of GRK4, which inhibited autophagy by increasing HDAC4 phosphorylation and decreasing its binding to the beclin-1 promoter. HDAC4 S632A mutation partially restored the GRK4-induced inhibition of autophagy. MI caused greater impairment of cardiac function in patients carrying the GRK4 A486V variant than in WT carriers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>GRK4 increases cardiomyocyte injury during MI by inhibiting autophagy and promoting cardiomyocyte apoptosis. These effects are mediated by the phosphorylation of HDAC4 and a decrease in beclin-1 expression.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehaa878","type":"journal-article","created":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T19:23:42Z","timestamp":1602703422000},"page":"1415-1430","source":"Crossref","is-referenced-by-count":43,"title":["The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0501-632X","authenticated-orcid":false,"given":"Liangpeng","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8841-4018","authenticated-orcid":false,"given":"Zhi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luxun","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dezhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewei","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andi","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military 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Ross Hall, Suite 745C, 2300 I Street, N.W. Washington, DC 20037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8958-1088","authenticated-orcid":false,"given":"Ken","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8315-2362","authenticated-orcid":false,"given":"Wei Eric","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Daping Hospital, Third Military Medical University , Chongqing, China"},{"name":"Chongqing Key Laboratory for Hypertension Research, Chongqing Cardiovascular Clinical Research Center, Chongqing Institute of Cardiology , Chongqing, China"},{"name":"State 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