Apocynin Attenuates Cardiac Injury in Type 4 Cardiorenal Syndrome via Suppressing Cardiac Fibroblast Growth Factor-2 With Oxidative Stress Inhibition

Background: type 4 cardiorenal syndrome (crs) refers to the cardiac injury induced by chronic kidney disease. we aimed to assess oxidative stress and cardiac injury in patients with type 4 crs,determine whether the antioxidant apocynin attenuated cardiac injury in rats with type 4 crs,and explore potential mechanisms.methods and results: a cross-sectional study was conducted among patients with type 4 crs (n=17) and controls (n=16). compared with controls,patients with type 4 crs showed elevated oxidative stress,which was significantly correlated with cardiac hypertrophy and decreased ejection fraction. in vivo study,male sprague-dawley rats underwent 5/6 subtotal nephrectomy and sham surgery,followed with apocynin or vehicle treatment for 8 weeks. eight weeks after surgery,the 5/6 subtotal nephrectomy rats mimicked type 4 crs,showing increased serum creatinine,cardiac hypertrophy and fibrosis,and decreased ejection fraction compared with sham-operated animals. cardiac malondialdehyde,nadph oxidase activity,fibroblast growth factor-2,and extracellular signal-regulated 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 ii-induced nadph oxidase-dependent oxidative stress,upregulation of fibroblast growth factor-2 and fibrosis biomarkers,and erk1/2 phosphorylation in cardiac fibroblasts. importantly,the erk1/2 inhibitor u0126 reduced the upregulation of fibroblast growth factor-2 and fibrosis biomarkers in angiotensin ii-treated fibroblasts.conclusions: oxidative stress is a candidate mediator for type 4 crs. apocynin attenuated cardiac injury in type 4 crs rats via inhibiting nadph oxidase-dependent oxidative stress-activated erk1/2 pathway and subsequent fibroblast growth factor-2 upregulation. our study added evidence to the beneficial effect of apocynin in type 4 crs. © 2015 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.