{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T15:18:13Z","timestamp":1781191093695,"version":"3.54.1"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,7,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Type 4 cardiorenal syndrome (\n              <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n              ) refers to the cardiac injury induced by chronic kidney disease. We aimed to assess oxidative stress and cardiac injury in patients with type 4\n              <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n              , determine whether the antioxidant apocynin attenuated cardiac injury in rats with type 4\n              <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n              , and explore potential mechanisms.\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              A cross\u2010sectional study was conducted among patients with type 4\n              <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n              (n=17) and controls (n=16). Compared with controls, patients with type 4\n              <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n              showed elevated oxidative stress, which was significantly correlated with cardiac hypertrophy and decreased ejection fraction. In vivo study, male Sprague\u2010Dawley rats underwent 5\/6 subtotal nephrectomy and sham surgery, followed with apocynin or vehicle treatment for 8\u00a0weeks. Eight weeks after surgery, the 5\/6 subtotal nephrectomy rats mimicked type 4\n              <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n              , showing increased serum creatinine, cardiac hypertrophy and fibrosis, and decreased ejection fraction compared with sham\u2010operated animals. Cardiac malondialdehyde,\n              <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content>\n              oxidase activity, fibroblast growth factor\u20102, and extracellular signal\u2010regulated kinase 1\/2 (ERK1\/2) phosphorylation increased significantly in the 5\/6 subtotal nephrectomy rats. These changes were significantly attenuated by apocynin. In vitro study showed that apocynin reduced angiotensin\n              <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n              \u2013induced\n              <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content>\n              oxidase\u2013dependent oxidative stress, upregulation of fibroblast growth factor\u20102 and fibrosis biomarkers, and\n              <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n              1\/2 phosphorylation in cardiac fibroblasts. Importantly, the\n              <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n              1\/2 inhibitor U0126 reduced the upregulation of fibroblast growth factor\u20102 and fibrosis biomarkers in angiotensin\n              <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content>\n              \u2013treated fibroblasts.\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              Oxidative stress is a candidate mediator for type 4\n              <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n              . Apocynin attenuated cardiac injury in type 4\n              <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n              rats via inhibiting\n              <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content>\n              oxidase\u2013dependent oxidative stress\u2010activated\n              <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>\n              1\/2 pathway and subsequent fibroblast growth factor\u20102 upregulation. Our study added evidence to the beneficial effect of apocynin in type 4\n              <jats:styled-content style=\"fixed-case\">CRS<\/jats:styled-content>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.114.001598","type":"journal-article","created":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T19:04:02Z","timestamp":1536951842000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["Apocynin Attenuates Cardiac Injury in Type 4 Cardiorenal Syndrome via Suppressing Cardiac Fibroblast Growth Factor\u20102 With Oxidative Stress Inhibition"],"prefix":"10.1161","volume":"4","author":[{"given":"Yang","family":"Liu","sequence":"first","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital of Sun Yat\u2010sen University, Guangzhou, China"},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China"},{"name":"Department of Cardiology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, The Third Affiliated Hospital of Sun Yat\u2010sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital of Sun Yat\u2010sen University, Guangzhou, China"},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital of Sun Yat\u2010sen University, Guangzhou, China"},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Huang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital of Sun Yat\u2010sen University, Guangzhou, China"},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital of Sun Yat\u2010sen University, Guangzhou, China"},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanchun","family":"Tang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital of Sun Yat\u2010sen University, Guangzhou, China"},{"name":"Weil Institute of Critical Care Medicine, Rancho Mirage, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Huang","sequence":"additional","affiliation":[{"name":"Sun Yat\u2010sen Memorial Hospital of Sun Yat\u2010sen University, Guangzhou, China"},{"name":"Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, 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