ArticleCardiovascular research2021
NADPH oxidase-4 promotes eccentric cardiac hypertrophy in response to volume overload.
Article in Cardiovascular research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- The Dual Role of NOX4 in Cardiovascular Diseases: Driver of Oxidative Stress and Mediator of Adaptive Remodeling.Antioxidants (Basel, Switzerland) · 2025Review
- Jaranol: a compound with therapeutic activity against pathological cardiac remodelling via multi-target inhibition of the Snai3/TLR2 and NF-κB signaling pathways.Frontiers in pharmacology · 2025Article
- USP20 deletion promotes eccentric cardiac remodeling in response to pressure overload and increases mortality.American journal of physiology. Heart and circulatory physiology · 2024Article
- NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors.Journal of medicinal chemistry · 2023Review
- (Pro)Renin Receptor Decoy Peptide PRO20 Protects against Oxidative Renal Damage Induced by Advanced Oxidation Protein Products.Molecules (Basel, Switzerland) · 2023Article
- Role of c-Src and reactive oxygen species in cardiovascular diseases.Molecular genetics and genomics : MGG · 2023Review
- Functional remodelling of perinuclear mitochondria alters nucleoplasmic CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Article
- Anti-Diabetic Therapy, Heart Failure and Oxidative Stress: An Update.Journal of clinical medicine · 2022Review
- Ca2+/calmodulin-dependent protein kinase II and protein kinase G oxidation contributes to impaired sarcomeric proteins in hypertrophy model.ESC heart failure · 2022Article
- Canagliflozin mitigates ferroptosis and ameliorates heart failure in rats with preserved ejection fraction.Naunyn-Schmiedeberg's archives of pharmacology · 2022Article
- Chronic Coronary Syndrome in Frail Old Population.Life (Basel, Switzerland) · 2022Review
- Left Ventricular SGLT1 Protein Expression Correlates with the Extent of Myocardial Nitro-Oxidative Stress in Rats with Pressure and Volume Overload-Induced Heart Failure.Antioxidants (Basel, Switzerland) · 2021Article
- Endothelial NADPH oxidase 4 protects against angiotensin II-induced cardiac fibrosis and inflammation.ESC heart failure · 2021Article
- Targeting cardiac fibrosis in heart failure with preserved ejection fraction: mirage or miracle?EMBO molecular medicine · 2020Review
- Left ventricular response in the transition from hypertrophy to failure recapitulates distinct roles of Akt, β-arrestin-2, and CaMKII in mice with aortic regurgitation.Annals of translational medicine · 2020Article
- Angiotensin II Decreases Endothelial Nitric Oxide Synthase PhosphorylationFrontiers in physiology · 2020Article
- Characterization of the Oxidative Stress in Renal Ischemia/Reperfusion-Induced Cardiorenal Syndrome Type 3.BioMed research international · 2020Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsChronic pressure or volume overload induce concentric vs. eccentric left ventricular (LV) remodelling, respectively. Previous studies suggest that distinct signalling pathways are involved in these responses. NADPH oxidase-4 (Nox4) is a reactive oxygen species-generating enzyme that can limit detrimental cardiac remodelling in response to pressure overload. This study aimed to assess its role in volume overload-induced remodelling. METHODS AND
resultsWe compared the responses to creation of an aortocaval fistula (Shunt) to induce volume overload in Nox4-null mice (Nox4-/-) vs. wild-type (WT) littermates. Induction of Shunt resulted in a significant increase in cardiac Nox4 mRNA and protein levels in WT mice as compared to Sham controls. Nox4-/- mice developed less eccentric LV remodelling than WT mice (echocardiographic relative wall thickness: 0.30 vs. 0.27, P < 0.05), with less LV hypertrophy at organ level (increase in LV weight/tibia length ratio of 25% vs. 43%, P < 0.01) and cellular level (cardiomyocyte cross-sectional area: 323 µm2 vs. 379 μm2, P < 0.01). LV ejection fraction, foetal gene expression, interstitial fibrosis, myocardial capillary density, and levels of myocyte apoptosis after Shunt were similar in the two genotypes. Myocardial phospho-Akt levels were increased after induction of Shunt in WT mice, whereas levels decreased in Nox4-/- mice (+29% vs. -21%, P < 0.05), associated with a higher level of phosphorylation of the S6 ribosomal protein (S6) and the eIF4E-binding protein 1 (4E-BP1) in WT compared to Nox4-/- mice. We identified that Akt activation in cardiac cells is augmented by Nox4 via a Src kinase-dependent inactivation of protein phosphatase 2A.
conclusionEndogenous Nox4 is required for the full development of eccentric cardiac hypertrophy and remodelling during chronic volume overload. Nox4-dependent activation of Akt and its downstream targets S6 and 4E-BP1 may be involved in this effect.
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