ArticleCardiovascular research2011
Phosphodiesterase-5A (PDE5A) is localized to the endothelial caveolae and modulates NOS3 activity.
Article in Cardiovascular research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- Sildenafil improves vascular endothelial function in patients with cystic fibrosis.American journal of physiology. Heart and circulatory physiology · 2018Trial
- Sildenafil increases muscle protein synthesis and reduces muscle fatigue.Clinical and translational science · 2013Trial
- Assessing the therapeutic potential of PDE-5 inhibitors in adults: Insights from a multi-omics study.Physiological reports · 2026Article
- Phosphodiesterase inhibitors as emerging therapeutics for skeletal disorders: A comprehensive review of mechanisms and repurposing potential.Bone reports · 2026Review
- Protective Effect of Paeoniae Radix Alba Carbonisata on Hepatic Amyloidosis by Regulating Calcium Homeostasis.International journal of molecular sciences · 2026Article
- Endothelial miR-7052 Safeguards Blood-Brain Barrier Integrity During Endotoxemia by Co-repressing ANGPT2 and PDE5A.Molecular neurobiology · 2026Article
- Icariin targets PDE5A to regulate viability, DNA synthesis and DNA damage of spermatogonial stem cells and improves reproductive capacity.Asian journal of andrology · 2025Article
- Phosphodiesterase 5A regulates the vomeronasal pump in mice.Genesis (New York, N.Y. : 2000) · 2024Article
- Identification of Transcripts with Shared Roles in the Pathogenesis of Postmenopausal Osteoporosis and Cardiovascular Disease.International journal of molecular sciences · 2024Article
- Phosphodiesterase in heart and vessels: from physiology to diseases.Physiological reviews · 2024Review
- Genetic determinants of blood pressure and heart rate identified through ENU-induced mutagenesis with automated meiotic mapping.Science advances · 2024Article
- Genetic insight into putative causes of xanthelasma palpebrarum: a Mendelian randomization study.Frontiers in immunology · 2024Article
- Article
- The rs2682826 Polymorphism of theLife (Basel, Switzerland) · 2023Article
- Genomic Analyses for Selective Signatures and Genes Involved in Hot Adaptation Among Indigenous Chickens From Different Tropical Climate Regions.Frontiers in genetics · 2022Article
- Seeking Illumination: The Path to Chemiluminescent 1,2-Dioxetanes for Quantitative Measurements andAccounts of chemical research · 2021Article
- Cardiac Cyclic Nucleotide Phosphodiesterases: Roles and Therapeutic Potential in Heart Failure.Cardiovascular drugs and therapy · 2020Review
- Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress.The journal of sexual medicine · 2019Article
- Altered Penile Caveolin Expression in Diabetes: Potential Role in Erectile Dysfunction.The journal of sexual medicine · 2017Article
- Phosphodiesterase Type 5 Inhibitor Sildenafil Decreases the Proinflammatory Chemokine CXCL10 in Human Cardiomyocytes and in Subjects with Diabetic Cardiomyopathy.Inflammation · 2016Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
aimsIt has been well demonstrated that phosphodiesterase-5A (PDE5A) is expressed in smooth muscle cells and plays an important role in regulation of vascular tone. The role of endothelial PDE5A, however, has not been yet characterized. The present study was undertaken to determine the presence, localization, and potential physiologic significance of PDE5A within vascular endothelial cells. METHODS AND
resultsWe demonstrate primary location of human, mouse, and bovine endothelial PDE5A at or near caveolae. We found that the spatial localization of PDE5A at the level of caveolin-rich lipid rafts allows for a feedback loop between endothelial PDE5A and nitric oxide synthase (NOS3). Treatment of human endothelium with PDE5A inhibitors resulted in a significant increase in NOS3 activity, whereas overexpression of PDE5A using an adenoviral vector, both in vivo and in cell culture, resulted in decreased NOS3 activity and endothelium-dependent vasodilation. The molecular mechanism responsible for these interactions is primarily regulated by cGMP-dependent second messenger. PDE5A overexpression also resulted in a significant decrease in protein kinase 1 (PKG1) activity. Overexpression of PKG1 rapidly activated NOS3, whereas silencing of the PKG1 gene with siRNA inhibited both NOS3 phosphorylation (S1179) and activity, indicating a novel role for PKG1 in direct regulation of NOS3.
conclusionOur data collectively suggest another target for PDE5A inhibition in endothelial dysfunction and provide another physiologic significance for PDE5A in the modulation of endothelial-dependent flow-mediated vasodilation. Using both in vitro and in vivo models, as well as human data, we show that inhibition of endothelial PDE5A improves endothelial function.
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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.