{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T14:20:35Z","timestamp":1778682035819,"version":"3.51.4"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,5,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Maladaptive cardiac hypertrophy is a major risk factor for heart failure, which is the leading cause of death worldwide.\n              <jats:styled-content style=\"fixed-case\">C\u2010C<\/jats:styled-content>\n              motif chemokine receptor 9 (\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9), a subfamily of the G protein\u2013coupled receptor supergene family, has been highlighted as an immunologic regulator in the development and homing of immune cells and in immune\u2010related diseases. Recently,\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9 was found to be involved in the pathogenesis of other diseases such as cardiovascular diseases; however, the effects that\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9 exerts in cardiac hypertrophy remain elusive.\n            <\/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\">\n              We observed significantly increased\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9 protein levels in failing human hearts and in a mouse or cardiomyocyte hypertrophy model. In loss\u2010 and gain\u2010of\u2010function experiments, we found that pressure overload\u2013induced hypertrophy was greatly attenuated by\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9 deficiency in cardiac\u2010specific\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9 knockout mice, whereas\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9 overexpression in cardiac\u2010specific transgenic mice strikingly enhanced cardiac hypertrophy. The prohypertrophic effects of\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9 were also tested in\u00a0vitro, and a similar phenomenon was observed. Consequently, we identified a causal role for\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9 in pathological cardiac hypertrophy. Mechanistically, we revealed a lack of difference in the expression levels of mitogen\u2010activated protein kinases between groups, whereas the phosphorylation of\n              <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>\n              \/protein kinase B and downstream effectors significantly decreased in\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9 knockout mice and increased in\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9\n              <jats:styled-content style=\"fixed-case\">transgenic<\/jats:styled-content>\n              mice after aortic binding surgery.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The prohypertrophic effects of\n              <jats:styled-content style=\"fixed-case\">CCR<\/jats:styled-content>\n              9 were not attributable to the\n              <jats:styled-content style=\"fixed-case\">mitogen\u2010activated protein kinase<\/jats:styled-content>\n              signaling pathway but rather to the\n              <jats:styled-content style=\"fixed-case\">AKT<\/jats:styled-content>\n              \u2013mammalian target of rapamycin\u2013glycogen synthase kinase 3\u03b2 signaling cascade.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.003342","type":"journal-article","created":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T04:20:17Z","timestamp":1462422017000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["C\u2010C Motif Chemokine Receptor 9 Exacerbates Pressure Overload\u2013Induced Cardiac Hypertrophy and Dysfunction"],"prefix":"10.1161","volume":"5","author":[{"given":"Zhengxi","family":"Xu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanghua","family":"Mei","sequence":"additional","affiliation":[{"name":"Animal Experiment Center and Animal Biosafety Level\u2010III Laboratory, Wuhan University, Wuhan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanning","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Sun","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China"},{"name":"Department of Cardiac Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 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