ArticleCirculation2010
Oxidative stress regulates left ventricular PDE5 expression in the failing heart.
Article in Circulation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 166 citations in OpenAlex.
- Effects of tadalafil administration on plasma markers of exercise-induced muscle damage, IL6 and antioxidant status capacity.European journal of applied physiology · 2015Trial
- Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy.Annals of neurology · 2014Trial
- PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in Diastolic Heart Failure (RELAX) trial: rationale and design.Circulation. Heart failure · 2012Trial
- Redox Imbalance and NOS-Dependent Modulation of Superoxide in the Bladder Mucosa of Women With IC/BPS: A Preliminary Study.Journal of cellular and molecular medicine · 2026Article
- Systolic pressure overload caused pulmonary oxidative stress, vessel remodeling and severe microvascular thrombosis in CD40 knockout mice through promoting platelet aggregation.Redox biology · 2026Article
- 4E-BP inhibition ameliorates heart failure through translational upregulation of SERCA2a and modulation of mitochondrial redox signaling in cardiomyocytes.Redox biology · 2026Article
- Genetic inhibition of IL-12β suppresses systolic overload-induced cardiac oxidative stress, inflammation, and heart failure development.Redox biology · 2026Article
- Nitric Oxide Signaling and Sensing in Age-Related Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- The impact of phosphodiesterase-5 inhibition or angiotensin-converting enzyme inhibition on right and left ventricular remodeling in heart failure due to chronic volume overload.Pharmacology research & perspectives · 2024Article
- Cardiac Effects of Phosphodiesterase-5 Inhibitors: Efficacy and Safety.Cardiovascular drugs and therapy · 2023Review
- Changes in Left Ventricular Ejection Fraction and Oxidative Stress after Phosphodiesterase Type-5 Inhibitor Treatment in an Experimental Model of Retrograde Rat Perfusion.Medicina (Kaunas, Lithuania) · 2023Article
- Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension: Focus on Phosphodiesterase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Inhibition of GCN2 Alleviates Cardiomyopathy in Type 2 Diabetic Mice via Attenuating Lipotoxicity and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2022Article
- Investigation into the protective effects of hypaconitine and glycyrrhetinic acid against chronic heart failure of the rats.BMC complementary medicine and therapies · 2022Article
- Phosphodiesterases and Compartmentation of cAMP and cGMP Signaling in Regulation of Cardiac Contractility in Normal and Failing Hearts.International journal of molecular sciences · 2022Review
- Article
- Long-Term PDE-5A Inhibition Improves Myofilament Function in Left and Right Ventricular Cardiomyocytes through Partially Different Mechanisms in Diabetic Rat Hearts.Antioxidants (Basel, Switzerland) · 2021Article
- Hypertrophy-Reduced Autophagy Causes Cardiac Dysfunction by Directly Impacting Cardiomyocyte Contractility.Cells · 2021Article
- An update of cyclic nucleotide phosphodiesterase as a target for cardiac diseases.Expert opinion on drug discovery · 2021Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPhosphodiesterase type 5 (PDE5) inhibition has been shown to exert profound beneficial effects in the failing heart, suggesting a significant role for PDE5 in the development of congestive heart failure (CHF). The purpose of this study is to test the hypothesis that oxidative stress causes increased PDE5 expression in cardiac myocytes and that increased PDE5 contributes to the development of CHF. METHODS AND
resultsMyocardial PDE5 expression and cellular distribution were determined in left ventricular samples from patients with end-stage CHF and normal donors and from mice after transverse aortic constriction (TAC)-induced CHF. Compared with donor human hearts, myocardial PDE5 protein was increased approximately equal 4.5-fold in CHF samples, and the increase of myocardial PDE5 expression was significantly correlated with myocardial oxidative stress markers 3'-nitrotyrosine or 4-hydroxynonenal expression (P<0.05). Histological examination demonstrated that PDE5 was mainly expressed in vascular smooth muscle in normal donor hearts, but its expression was increased in both cardiac myocytes and vascular smooth muscle of CHF hearts. Myocardial PDE5 protein content and activity also increased in mice after TAC-induced CHF (P<0.05). When the superoxide dismutase (SOD) mimetic M40401 was administered to attenuate oxidative stress, the increased PDE5 protein and activity caused by TAC was blunted, and the hearts were protected against left ventricular hypertrophy and CHF. Conversely, increased myocardial oxidative stress in superoxide dismutase 3 knockout mice caused a greater increase of PDE5 expression and CHF after TAC. In addition, administration of sildenafil to inhibit PDE5 attenuated TAC-induced myocardial oxidative stress, PDE5 expression, and CHF.
conclusionsMyocardial oxidative stress increases PDE5 expression in the failing heart. Reducing oxidative stress by treatment with M40401 attenuated cardiomyocyte PDE5 expression. This and selective inhibition of PDE5 protected the heart against pressure overload-induced left ventricular hypertrophy and CHF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.