{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:14:21Z","timestamp":1792066461473,"version":"4.4.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,9,24]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>\n              Cardiac hypertrophy and subsequent heart failure triggered by chronic hypertension represent major challenges for cardiovascular research. Beyond neurohormonal and myocyte signaling pathways, growing evidence suggests inflammatory signaling pathways as therapeutically targetable contributors to this process. We recently reported that\n              <jats:italic>microRNA-155<\/jats:italic>\n              is a key mediator of cardiac inflammation and injury in infectious myocarditis. Here, we investigated the impact of\n              <jats:italic>microRNA-155<\/jats:italic>\n              manipulation in hypertensive heart disease.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Genetic loss or pharmacological inhibition of the leukocyte-expressed\n              <jats:italic>microRNA-155<\/jats:italic>\n              in mice markedly reduced cardiac inflammation, hypertrophy, and dysfunction on pressure overload. These alterations were macrophage dependent because in vivo cardiomyocyte-specific\n              <jats:italic>microRNA-155<\/jats:italic>\n              manipulation did not affect cardiac hypertrophy or dysfunction, whereas bone marrow transplantation from wild-type mice into\n              <jats:italic>microRNA-155<\/jats:italic>\n              knockout animals rescued the hypertrophic response of the cardiomyocytes and vice versa. In vitro, media from\n              <jats:italic>microRNA-155<\/jats:italic>\n              knockout macrophages blocked the hypertrophic growth of stimulated cardiomyocytes, confirming that macrophages influence myocyte growth in a\n              <jats:italic>microRNA-155<\/jats:italic>\n              -dependent paracrine manner. These effects were at least partly mediated by the direct\n              <jats:italic>microRNA-155<\/jats:italic>\n              target suppressor of cytokine signaling 1 (Socs1) because Socs1 knockdown in\n              <jats:italic>microRNA-155<\/jats:italic>\n              knockout macrophages largely restored their hypertrophy-stimulating potency.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Our findings reveal that\n              <jats:italic>microRNA-155<\/jats:italic>\n              expression in macrophages promotes cardiac inflammation, hypertrophy, and failure in response to pressure overload. These data support the causative significance of inflammatory signaling in hypertrophic heart disease and demonstrate the feasibility of therapeutic microRNA targeting of inflammation in heart failure.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.112.001357","type":"journal-article","created":{"date-parts":[[2013,8,17]],"date-time":"2013-08-17T04:24:23Z","timestamp":1376713463000},"page":"1420-1432","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":227,"title":["Macrophage MicroRNA-155 Promotes Cardiac Hypertrophy and Failure"],"prefix":"10.1161","volume":"128","author":[{"given":"Stephane","family":"Heymans","sequence":"first","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maarten F.","family":"Corsten","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Verhesen","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Carai","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick E.W.","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Custers","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Peters","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Hazebroek","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauran","family":"St\u00f6ger","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin","family":"Wijnands","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben J.","family":"Janssen","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther E.","family":"Creemers","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigal M.","family":"Pinto","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Grimm","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Sch\u00fcrmann","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vigorito","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Thum","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Stassen","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoke","family":"Yin","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mayr","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon J.","family":"de Windt","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Lutgens","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristiaan","family":"Wouters","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menno P.J.","family":"de Winther","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Zacchigna","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Giacca","sequence":"additional","affiliation":[{"name":"From the Center for Heart Failure Research, Department of Cardiology (S.H., M.F.C., W.V., P.C., R.E.W.v.L., K.C., T.P., M.H., M.v.B., A.-P.P., B.S.), Department of Molecular Genetics (L.S., M.P.J.d.W.), Department of Pathology (E.W., E.L.), Department of Pharmacology (B.J.J.), Department of Cardiology (L.J.d.W.), and Department of Internal Medicine (K.W.), Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands; Interuniversity Cardiology Institute of the..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"van Bilsen","sequence":"additional","affiliation":[{"name":"From 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