ArticleFrontiers in physiology2017
Alternative Splicing of NOX4 in the Failing Human Heart.
Article in Frontiers in physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Viral Comorbidities Remodel Host Transcriptome and Redox Signaling in an NADPH Oxidase Isoform-Specific Manner.Viruses · 2026Review
- Mitochondrial remodeling in heart failure with reduced ejection fraction.Frontiers in physiology · 2026Review
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling.Antioxidants (Basel, Switzerland) · 2025Review
- The Role of AMPKα in the Mechanism of Development and Treatment of Heart Failure.Reviews in cardiovascular medicine · 2025Review
- Beyond conventional therapy: NOX4 as a promising target in cardiomyopathy.Molecular biology reports · 2025Review
- Sirtuin 4 accelerates heart failure development by enhancing reactive oxygen species-mediated profibrotic transcriptional signaling.Journal of molecular and cellular cardiology plus · 2025Article
- Transcriptomic Alterations in Spliceosome Components in Advanced Heart Failure: Status of Cardiac-Specific Alternative Splicing Factors.International journal of molecular sciences · 2024Article
- A common gene signature of the right ventricle in failing rat and human hearts.Nature cardiovascular research · 2024Article
- The Association Between Oxidative Stress and the Progression of Heart Failure: A Systematic Review.Cureus · 2024Review
- Article
- Knockdown of ANGPTL2 promotes left ventricular systolic dysfunction by upregulation of NOX4 in mice.Frontiers in physiology · 2024Article
- NADPH Oxidases and Oxidative Stress in the Pathogenesis of Atrial Fibrillation.Antioxidants (Basel, Switzerland) · 2023Review
- Modeling Duchenne Muscular Dystrophy Cardiomyopathy with Patients' Induced Pluripotent Stem-Cell-Derived Cardiomyocytes.International journal of molecular sciences · 2023Review
- Human Resistin Induces Cardiac Dysfunction in Pulmonary Hypertension.Journal of the American Heart Association · 2023Article
- The regulation of cardiac intermediary metabolism by NADPH oxidases.Cardiovascular research · 2023Review
- Saxagliptin Cardiotoxicity in Chronic Heart Failure: The Role of DPP4 in the Regulation of Neuropeptide Tone.Biomedicines · 2022Article
- PACAP-38 and PAC1 Receptor Alterations in Plasma and Cardiac Tissue Samples of Heart Failure Patients.International journal of molecular sciences · 2022Article
- Human iPSC model reveals a central role for NOX4 and oxidative stress in Duchenne cardiomyopathy.Stem cell reports · 2022Article
- Interplay of Oxidative Stress and Necrosis-like Cell Death in Cardiac Ischemia/Reperfusion Injury: A Focus on Necroptosis.Biomedicines · 2022Review
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Authors and funding
16 authors at 6 institutions in 5 countries.
Funding
Abstract
Increased oxidative stress is a major contributor to the development and progression of heart failure, however, our knowledge on the role of the distinct NADPH oxidase (NOX) isoenzymes, especially on NOX4 is controversial. Therefore, we aimed to characterize NOX4 expression in human samples from healthy and failing hearts. Explanted human heart samples (left and right ventricular, and septal regions) were obtained from patients suffering from heart failure of ischemic or dilated origin. Control samples were obtained from donor hearts that were not used for transplantation. Deep RNA sequencing of the cardiac transcriptome indicated extensive alternative splicing of the NOX4 gene in heart failure as compared to samples from healthy donor hearts. Long distance PCR analysis with a universal 5'-3' end primer pair, allowing amplification of different splice variants, confirmed the presence of the splice variants. To assess translation of the alternatively spliced transcripts we determined protein expression of NOX4 by using a specific antibody recognizing a conserved region in all variants. Western blot analysis showed up-regulation of the full-length NOX4 in ischemic cardiomyopathy samples and confirmed presence of shorter isoforms both in control and failing samples with disease-associated expression pattern. We describe here for the first time that NOX4 undergoes extensive alternative splicing in human hearts which gives rise to the expression of different enzyme isoforms. The full length NOX4 is significantly upregulated in ischemic cardiomyopathy suggesting a role for NOX4 in ROS production during heart failure.
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