{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:17:50Z","timestamp":1792977470014,"version":"4.5.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,1,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">ADRB1 (adrenergic receptor beta 1) responds to neuroendocrine stimulations, which have great implications in hypertension. GRK2 (G protein\u2010coupled receptor kinase 2) is an essential regulator for many G protein\u2010coupled receptors and subsequent cell signaling cascades, but its role as a regulator of ADRB1 and associated cardiac hypertrophy in hypertension remains to be elucidated.<\/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\">In this study, we found the expressions of GRK2 and ADRB1 in peripheral blood mononuclear cells were positively associated with blood pressure levels in hypertensive patients and with their expression in heart. In vitro evidence showed a direct interaction in ADRB1 and GRK2 and genetic depletion of GRK2 blocks epinephrine\u2010induced upregulation of hypertrophic and fibrotic genes in cardiomyocytes. Meanwhile, we discovered a selective serotonin reuptake inhibitor paroxetine specifically blockades GRK2 and ADRB1 interaction. In vivo, paroxetine treatment ameliorates hypertension\u2010induced cardiac hypertrophy, dysfunction, and fibrosis in animal models. We found that paroxetine suppressed sympathetic overdrive and increased the adrenergic receptor sensitivity to catecholamines. Paroxetine treatment also blocks epinephrine\u2010induced upregulation of hypertrophic and fibrotic genes as well as ADRB1 internalization in cardiomyocytes. Coadministration of paroxetine further potentiates metoprolol\u2010induced reductions in blood pressure and heart rate, further attenuating cardiac hypertrophy in spontaneously hypertensive rats. Furthermore, in patients with hypertension accompanied with depression, we observed that cardiac remodeling was less severe in those with paroxetine treatment compared with those with other types of anti\u2010depressive agents.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Paroxetine promotes ADRB1 sensitivity and attenuates cardiac hypertrophy partially via blocking GRK2\u2010mediated ADRB1 activation and internalization in the context of hypertension.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.016364","type":"journal-article","created":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T12:19:03Z","timestamp":1609244343000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Paroxetine Attenuates Cardiac Hypertrophy Via Blocking GRK2 and ADRB1 Interaction in Hypertension"],"prefix":"10.1161","volume":"10","author":[{"given":"Xuejing","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Cardiology The Third Xiangya HospitalCentral South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengli","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology The Third Xiangya HospitalCentral South University Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaiyan","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Zhejiang Hospital Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Huang","sequence":"additional","affiliation":[{"name":"Ningbo Medical Center Lihuili Hospital Ningbo 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