{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:42:46Z","timestamp":1791193366238,"version":"4.1.0"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2010,6,11]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:underline>Rationale<\/jats:underline>\n                        :\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    Myocardial infarction (MI)-induced heart failure is characterized by central nervous system\u2013driven sympathoexcitation and deteriorating cardiac function. The paraventricular nucleus (PVN) of the hypothalamus is a key regulator of sympathetic nerve activity and is implicated in heart failure. Redox signaling in the PVN and other central nervous system sites is a primary mechanism of neuro-cardiovascular regulation, and excessive oxidant production by activation of NADPH oxidases (Noxs) is implicated in some neuro-cardiovascular diseases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:underline>Objective<\/jats:underline>\n                        :\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    We tested the hypothesis that Nox-mediated redox signaling in the PVN contributes to MI-induced sympathoexcitation and cardiac dysfunction in mice.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:underline>Methods and Results<\/jats:underline>\n                        :\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    Real-time PCR revealed that Nox4 was the most abundantly expressed Nox in PVN under basal conditions. Coronary arterial ligation (MI) caused a selective upregulation of this homolog compared to Nox1 and Nox2. Adenoviral gene transfer of Nox4 (AdsiNox4) to PVN (bilateral) attenuated MI-induced superoxide formation in this brain region (day 14) to the same level as that produced by PVN-targeted gene transfer of cytoplasmic superoxide dismutase (AdCu\/ZnSOD). MI mice treated with AdsiNox4 or AdCu\/ZnSOD in the PVN showed marked improvement in cardiac function as assessed by echocardiography and left ventricular hemodynamic analysis. This was accompanied by significantly diminished sympathetic outflow and apoptosis in the periinfarct region of the heart.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>\n                        <jats:underline>Conclusions<\/jats:underline>\n                        :\n                      <\/jats:italic>\n                    <\/jats:bold>\n                    These results suggest that MI causes dysregulation of Nox4-mediated redox signaling in the PVN, which leads to sympathetic overactivation and a decline in cardiac function. Targeted inhibition of oxidant signaling in the PVN could provide a novel treatment for MI-induced heart failure.\n                  <\/jats:p>","DOI":"10.1161\/circresaha.109.213025","type":"journal-article","created":{"date-parts":[[2010,4,22]],"date-time":"2010-04-22T22:47:02Z","timestamp":1271976422000},"page":"1763-1774","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":83,"title":["Silencing Nox4 in the Paraventricular Nucleus Improves Myocardial Infarction\u2013Induced Cardiac Dysfunction by Attenuating Sympathoexcitation and Periinfarct Apoptosis"],"prefix":"10.1161","volume":"106","author":[{"given":"David W.","family":"Infanger","sequence":"first","affiliation":[{"name":"From Biomedical Sciences (D.W.I., S.D.B., M.A.B., Y.Z., J.A.S., R.V.S., R.L.D.), College of Veterinary Medicine, Cornell University, Ithaca, NY; Department of Anatomy and Cell Biology (D.W.I.), University of Iowa, Iowa City; and Department of Cell &amp; Developmental Biology (X.C., R.V.S., R.L.D.), Weill Cornell Medical College, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian","family":"Cao","sequence":"additional","affiliation":[{"name":"From Biomedical Sciences (D.W.I., S.D.B., M.A.B., Y.Z., J.A.S., R.V.S., R.L.D.), College of Veterinary Medicine, Cornell University, Ithaca, NY; Department of Anatomy and Cell Biology (D.W.I.), University of Iowa, Iowa City; and Department of Cell &amp; Developmental Biology (X.C., R.V.S., R.L.D.), Weill Cornell Medical College, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Butler","sequence":"additional","affiliation":[{"name":"From Biomedical Sciences (D.W.I., S.D.B., M.A.B., Y.Z., J.A.S., R.V.S., R.L.D.), College of Veterinary Medicine, Cornell University, Ithaca, NY; Department of Anatomy and Cell Biology (D.W.I.), University of Iowa, Iowa City; and Department of Cell &amp; Developmental Biology (X.C., R.V.S., R.L.D.), Weill Cornell Medical College, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa A.","family":"Burmeister","sequence":"additional","affiliation":[{"name":"From Biomedical Sciences (D.W.I., S.D.B., M.A.B., Y.Z., J.A.S., R.V.S., R.L.D.), College of Veterinary Medicine, Cornell University, Ithaca, NY; Department of Anatomy and Cell Biology (D.W.I.), University of Iowa, Iowa City; and Department of Cell &amp; Developmental Biology (X.C., R.V.S., R.L.D.), Weill Cornell Medical College, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhou","sequence":"additional","affiliation":[{"name":"From Biomedical Sciences (D.W.I., S.D.B., M.A.B., Y.Z., J.A.S., R.V.S., R.L.D.), College of Veterinary Medicine, Cornell University, Ithaca, NY; Department of Anatomy and Cell Biology (D.W.I.), University of Iowa, Iowa City; and Department of Cell &amp; Developmental Biology (X.C., R.V.S., R.L.D.), Weill Cornell Medical College, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Stupinski","sequence":"additional","affiliation":[{"name":"From Biomedical Sciences (D.W.I., S.D.B., M.A.B., Y.Z., J.A.S., R.V.S., R.L.D.), College of Veterinary Medicine, Cornell University, Ithaca, NY; Department of Anatomy and Cell Biology (D.W.I.), University of Iowa, Iowa City; and Department of Cell &amp; Developmental Biology (X.C., R.V.S., R.L.D.), Weill Cornell Medical College, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram V.","family":"Sharma","sequence":"additional","affiliation":[{"name":"From Biomedical Sciences (D.W.I., S.D.B., M.A.B., Y.Z., J.A.S., R.V.S., R.L.D.), College of Veterinary Medicine, Cornell University, Ithaca, NY; Department of Anatomy and Cell Biology (D.W.I.), University of Iowa, Iowa City; and Department of Cell &amp; Developmental Biology (X.C., R.V.S., R.L.D.), Weill Cornell Medical College, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin L.","family":"Davisson","sequence":"additional","affiliation":[{"name":"From Biomedical Sciences (D.W.I., S.D.B., M.A.B., Y.Z., J.A.S., R.V.S., R.L.D.), College of Veterinary Medicine, Cornell University, Ithaca, NY; Department of Anatomy and Cell Biology (D.W.I.), University of Iowa, Iowa City; and Department of Cell &amp; Developmental Biology (X.C., R.V.S., R.L.D.), Weill Cornell Medical College, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.191261"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2006.04523.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.2003.01042.x"},{"key":"e_1_3_2_4_2","first-page":"R625","volume":"268","year":"1995","unstructured":"Bains JS, Ferguson AV. 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