{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T09:25:10Z","timestamp":1792661110629,"version":"4.5.0"},"reference-count":57,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2016,10,28]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>G protein\u2013coupled receptor kinase 2 (GRK2) is an important molecule upregulated after myocardial injury and during heart failure. Myocyte-specific GRK2 loss before and after myocardial ischemic injury improves cardiac function and remodeling. The cardiac fibroblast plays an important role in the repair and remodeling events after cardiac ischemia; the importance of GRK2 in these events has not been investigated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>The aim of this study is to elucidate the in vivo implications of deleting GRK2 in the cardiac fibroblast after ischemia\/reperfusion injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              We demonstrate, using Tamoxifen inducible, fibroblast-specific GRK2 knockout mice, that GRK2 loss confers a protective advantage over control mice after myocardial ischemia\/reperfusion injury. Fibroblast GRK2 knockout mice presented with decreased infarct size and preserved cardiac function 24 hours post ischemia\/reperfusion as demonstrated by increased ejection fraction (59.1\u00b11.8% versus 48.7\u00b11.2% in controls;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01). GRK2 fibroblast knockout mice also had decreased fibrosis and fibrotic gene expression. Importantly, these protective effects correlated with decreased infiltration of neutrophils to the ischemia site and decreased levels of tumor necrosis factor-\u03b1 expression and secretion in GRK2 fibroblast knockout mice.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>These novel data showing the benefits of inhibiting GRK2 in the cardiac fibroblast adds to previously published data showing the advantage of GRK2 ablation and reinforces the therapeutic potential of GRK2 inhibition in the heart after myocardial ischemia.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.116.309538","type":"journal-article","created":{"date-parts":[[2016,9,7]],"date-time":"2016-09-07T03:02:24Z","timestamp":1473217344000},"page":"1116-1127","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":93,"title":["Cardiac Fibroblast GRK2 Deletion Enhances Contractility and Remodeling Following Ischemia\/Reperfusion Injury"],"prefix":"10.1161","volume":"119","author":[{"given":"Meryl C.","family":"Woodall","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (M.C.W., B.P.W., E.G., A.Y., W.J.K.); and Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China (A.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin P.","family":"Woodall","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (M.C.W., B.P.W., E.G., A.Y., W.J.K.); and Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China (A.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (M.C.W., B.P.W., E.G., A.Y., W.J.K.); and Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China (A.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ancai","family":"Yuan","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (M.C.W., B.P.W., E.G., A.Y., W.J.K.); and Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China (A.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Koch","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology, Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA (M.C.W., B.P.W., E.G., A.Y., W.J.K.); and Department of Cardiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China (A.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.08.023"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.209809"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)00370-1"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.05.002"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2014.28"},{"key":"e_1_3_5_7_2","first-page":"476","article-title":"Signaling mechanisms regulating fibroblast activation, phenoconversion and fibrosis in the heart.","volume":"51","author":"MacLean J","year":"2014","unstructured":"MacLean J, Pasumarthi KB. 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