ArticleBritish journal of pharmacology2013
Chronic inhibition of cGMP-specific phosphodiesterase 5 suppresses endoplasmic reticulum stress in heart failure.
Article in British journal of pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Endoplasmic reticulum stress-mediated cell death in cardiovascular disease.Cell stress & chaperones · 2024Review
- Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Cardiac Effects of Phosphodiesterase-5 Inhibitors: Efficacy and Safety.Cardiovascular drugs and therapy · 2023Review
- Endoplasmic reticulum stress mediates homocysteine-induced hypertrophy of cardiac cells through activation of cyclic nucleotide phosphodiesterase 1C.Acta biochimica et biophysica Sinica · 2022Article
- Phosphodiesterase-5a Knock-out Suppresses Inflammation by Down-Regulating Adhesion Molecules in Cardiac Rupture Following Myocardial Infarction.Journal of cardiovascular translational research · 2021Article
- Nutraceutical, Dietary, and Lifestyle Options for Prevention and Treatment of Ventricular Hypertrophy and Heart Failure.International journal of molecular sciences · 2021Review
- Could Oral Phosphodiesterase 5 Inhibitors Have a Potential Adjuvant Role in Combating COVID-19 Infection?Sexual medicine reviews · 2021Review
- Pyrroloquinoline quinone attenuates isoproterenol hydrochloride‑induced cardiac hypertrophy in AC16 cells by inhibiting the NF‑κB signaling pathway.International journal of molecular medicine · 2020Article
- Swimming exercise inhibits myocardial ER stress in the hearts of aged mice by enhancing cGMP‑PKG signaling.Molecular medicine reports · 2020Article
- Phosphorylation Modifications Regulating Cardiac Protein Quality Control Mechanisms.Frontiers in physiology · 2020Review
- Involvement of natriuretic peptide system in C2C12 myocytes.Molecular and cellular biochemistry · 2019Article
- PDE5A Suppresses Proteasome Activity Leading to Insulin Resistance in C2C12 Myotubes.International journal of endocrinology · 2019Article
- Naringenin Attenuates Myocardial Ischemia-Reperfusion Injury via cGMP-PKGIOxidative medicine and cellular longevity · 2019Article
- Old dog, new tricks: novel cardiac targets and stress regulation by protein kinase G.Cardiovascular research · 2016Review
- Chemotherapeutic efficacy of phosphodiesterase inhibitors in chagasic cardiomyopathy.JACC. Basic to translational science · 2016Article
- Chronic heart failure: Ca(2+), catabolism, and catastrophic cell death.Biochimica et biophysica acta · 2016Review
- β-aminoisobutyric acid attenuates hepatic endoplasmic reticulum stress and glucose/lipid metabolic disturbance in mice with type 2 diabetes.Scientific reports · 2016Article
- Dapagliflozin attenuates cardiac remodeling and dysfunction in rats with β-adrenergic receptor overactivation through restoring calcium handling and suppressing cardiomyocyte apoptosis.Diabetes & vascular disease researchArticle
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeInhibition of the cGMP-specific phosphodiesterase 5 (PDE5) exerts profound beneficial effects on failing hearts. However, the mechanisms underlying the therapeutic effects of PDE5 inhibition on heart failure are unclear. The purpose of this study was to investigate whether PDE5 inhibition decreases endoplasmic reticulum (ER) stress, a key event in heart failure. EXPERIMENTAL APPROACH: Heart failure was induced by isoprenaline s.c. injection in Sprague-Dawley rats and transverse aortic constriction (TAC) in mice. PDE5 was inhibited with sildenafil. Heart function was detected by invasive pressure-volume analysis and echocardiography. ER stress markers were analysed by Western blotting. Apoptosis was measured by flow cytometric analysis. KEY
resultsPDE5 inhibition markedly attenuated isoprenaline-induced and TAC-induced cardiac hypertrophy and dysfunction, and reduced ER stress and apoptosis. Further, PDE5 inhibition with sildenafil largely prevented ER stress and reduced apoptosis in isoprenaline- or thapsigargin-treated cardiomyocytes. PKG inhibition markedly prevented the protective effects of sildenafil in vivo and in vitro. To further understand the mechanism of the effect of PDE5 inhibition on ER stress, we demonstrated that PDE5 inhibitor increased sarco-(endo)-plasmic reticulum Ca(2+) -ATPase activity via phosphorylation of phospholamban at Ser(16) . This may contribute to the attenuation of ER stress induced by PDE5 inhibition. CONCLUSION AND IMPLICATIONS: These results suggest that PDE5 inhibition can attenuate ER stress and improve cardiac function in vivo and in vitro. Suppression of ER stress by inhibiting PDE5 may contribute to the therapeutic effects on heart failure.
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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.