ArticleJournal of the American Heart Association2015
Apocynin Attenuates Cardiac Injury in Type 4 Cardiorenal Syndrome via Suppressing Cardiac Fibroblast Growth Factor-2 With Oxidative Stress Inhibition.
Article in Journal of the American Heart Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Cardiorenal Associations in Preclinical Modeling: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- Experimental rodent models of cardiorenal syndrome types 3 and 4: Insights and clinical relevance (Review).International journal of molecular medicine · 2026Review
- Recharging the Powerhouse: Mitochondrial Dysfunction and Therapy in Cardiorenal Syndrome Type 4.Current heart failure reports · 2025Review
- Cardiorenal syndrome: clinical diagnosis, molecular mechanisms and therapeutic strategies.Acta pharmacologica Sinica · 2025Review
- Renal-Cardiac Crosstalk in the Pathogenesis and Progression of Heart Failure.Circulation research · 2025Review
- [Anemia and heart failure with preserved ejection fraction in adult patients with cardiorenal syndrome: a cross-sectional study]Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina) · 2025Article
- Apocynin, a Selective NADPH Oxidase (Nox2) Inhibitor, Ameliorates Behavioural and Learning Deficits in the Fragile X Syndrome Mouse Model.Biomedicines · 2024Article
- Apocynin and Hyperbaric Oxygen Therapy Improve Renal Function and Structure in an Animal Model of CKD.Biomedicines · 2024Article
- Cardioprotective action of apocynin in isoproterenol-induced cardiac damage is mediated through Nrf-2/HO-1 signaling pathway.Food science & nutrition · 2024Article
- Panax notoginseng saponins inhibits NLRP3 inflammasome-mediated pyroptosis by downregulating lncRNA-ANRIL in cardiorenal syndrome type 4.Chinese medicine · 2023Article
- New Insight in Cardiorenal Syndrome: From Biomarkers to Therapy.International journal of molecular sciences · 2023Review
- Exercise Training Ameliorates Renal Oxidative Stress in Rats with Chronic Renal Failure.Metabolites · 2022Article
- Beyond the Cardiorenal Syndrome: Pathophysiological Approaches and Biomarkers for Renal and Cardiac Crosstalk.Diagnostics (Basel, Switzerland) · 2022Review
- ALKBH1-demethylated DNA N6-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney disease.The Journal of clinical investigation · 2021Article
- Oxidative Stress and Inflammation as Predictors of Mortality and Cardiovascular Events in Hemodialysis Patients: The DREAM Cohort.Journal of atherosclerosis and thrombosis · 2021Observational
- The Multifunctional Contribution of FGF Signaling to Cardiac Development, Homeostasis, Disease and Repair.Frontiers in cell and developmental biology · 2021Review
- Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212.Scientific reports · 2019Article
- Mechanisms and Modulation of Oxidative/Nitrative Stress in Type 4 Cardio-Renal Syndrome and Renal Sarcopenia.Frontiers in physiology · 2018Review
- Review
- FOXO1-suppressed miR-424 regulates the proliferation and osteogenic differentiation of MSCs by targeting FGF2 under oxidative stress.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundType 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
resultsA 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.
conclusionsOxidative 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.
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Registered trials
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