Affinage

PDE5A

cGMP-specific 3',5'-cyclic phosphodiesterase · UniProt O76074

Length
875 aa
Mass
100.0 kDa
Annotated
2026-06-10
56 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDE5A is a cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase that hydrolyzes cGMP to GMP, thereby setting the amplitude and duration of cGMP–PKG signaling across vascular, cardiac, platelet, and neuronal compartments (PMID:9714779, PMID:36252813). The gene is expressed as three isoforms (A1, A2, A3) generated from alternative first exons driven by distinct promoters that are bound by AP-2 and Sp1 and are positively reinforced by both cAMP and cGMP, constituting a feedback loop on enzyme expression (PMID:10679249, PMID:11896473). Subcellular targeting determines its physiological role: in vascular endothelial cells PDE5A resides in caveolin-rich lipid rafts where it forms a reciprocal feedback circuit with NOS3, with PKG1 directly controlling NOS3 phosphorylation at S1179 to tune endothelium-dependent vasodilation (PMID:21421555); in cardiomyocytes it localizes to the z-band in an eNOS-dependent manner and restrains β-adrenergic responses through a β3-adrenergic receptor→NOS→cGMP→PKG axis that phosphorylates troponin I at Ser23/Ser24 (PMID:18790048, PMID:20107996). By limiting intracellular cGMP, PDE5A is also a positive regulator of platelet activation, aggregation, and thrombus formation, opposing the VASP-phosphorylating cGMP brake (PMID:36252813). PDE5A expression is controlled at multiple levels: transcriptionally it is repressed by SMAD2/3 in myostatin signaling and by RUNX1 in vascular smooth muscle (PMID:35155444, PMID:41853865), post-transcriptionally it is targeted by miR-19a/b-3p at its 3'UTR (PMID:29664809), and post-translationally it is stabilized by the deubiquitinase OTUD1, which binds the GAF1 and PDEase domains and reverses K48-linked ubiquitin chains via its catalytic Cys320 to prevent proteasomal degradation (PMID:38185350). In cancer, oncogenic BRAF→MEK→BRN2 transcriptionally downregulates PDE5A to elevate cGMP and drive melanoma invasion, while PDE5A-expressing cancer-associated fibroblasts signal through PI3K/AKT/mTOR→CXCL12/CXCR4 to build an immunosuppressive microenvironment (PMID:21215707, PMID:41115748).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Establishing that PDE5A encodes a cGMP-binding, cGMP-specific phosphodiesterase defined its core enzymatic identity and the basis for selective inhibitor action.

    Evidence cDNA cloning with yeast expression and in vitro cGMP hydrolysis assay validated by selective PDE5 inhibitors zaprinast and DMPPO

    PMID:9714779

    Open questions at the time
    • Did not resolve isoform-specific catalytic differences
    • No structural basis for substrate specificity established
  2. 2000 Medium

    Mapping the gene architecture and isoform promoters showed how A1/A2/A3 variants arise and identified the transcription factors driving their expression.

    Evidence Genomic and RACE-PCR cloning, DNase I footprinting, and promoter-reporter assays defining alternative first exons and AP-2/Sp1 sites

    PMID:10679249 PMID:11162575 PMID:11896473 PMID:9716380

    Open questions at the time
    • Tissue-specific isoform usage not resolved
    • Functional distinctions between A1/A2/A3 proteins not established
  3. 2008 High

    Demonstrating z-band localization and a role in cardiomyocyte hypertrophy connected PDE5A's catalytic activity to spatial cGMP/PKG control in the heart.

    Evidence shRNA silencing, DsRed-PDE5 fusion imaging in adult myocytes, eNOS-/- background, and phenylephrine hypertrophy assays

    PMID:18790048

    Open questions at the time
    • Molecular anchor mediating z-band targeting not identified
    • Dependence on eNOS for localization not mechanistically explained
  4. 2010 High

    Defining the β3-AR→NOS→cGMP→PKG→troponin I Ser23/24 axis explained how PDE5A restrains acute β-adrenergic contractile responses.

    Evidence Sarcomere shortening video microscopy, β3-AR-/- mice, pharmacological inhibitors, and TnI phosphorylation analysis in slow-skeletal TnI myocytes

    PMID:20107996

    Open questions at the time
    • Whether the pathway operates identically in failing myocardium not addressed
    • Quantitative contribution relative to other PDEs not defined
  5. 2011 High

    Identifying caveolar localization and a NOS3/PKG1 feedback loop, alongside BRAF-driven suppression in melanoma, showed PDE5A acts as a compartmentalized cGMP gatekeeper with opposing roles in endothelium and cancer.

    Evidence Caveolin-rich raft fractionation, adenoviral overexpression and PKG1 siRNA in endothelial cells; siRNA/MEK inhibition/BRN2 knockdown with invasion and cGMP/Ca2+ readouts in melanoma

    PMID:21215707 PMID:21421555

    Open questions at the time
    • Mechanism anchoring PDE5A to caveolae not defined
    • Direct BRN2 binding to the PDE5A promoter not demonstrated
  6. 2014 Medium

    Mutagenesis of Ser102/Ser104 linked specific residues to PDE5A conformational state and catalytic activity, hinting at phosphorylation-dependent regulation.

    Evidence Site-directed mutagenesis with in vitro [3H]cGMP hydrolysis and native PAGE in GFP-fusion-expressing SK-N-AS cells

    PMID:25247292

    Open questions at the time
    • Physiological kinase phosphorylating these residues not identified
    • Effect in intact tissue not tested
  7. 2018 Medium

    Showing miR-19a/b-3p directly targets the PDE5A 3'UTR added a post-transcriptional layer of control with consequences for cardiac hypertrophy.

    Evidence 3'UTR luciferase reporter, miRNA transfection, and transgenic mice protected from Ang II-induced hypertrophy

    PMID:29664809

    Open questions at the time
    • Other miRNAs cooperating at the 3'UTR not mapped
    • Tissue specificity of miR-19a/b-3p regulation unclear
  8. 2020 Medium

    Extending PDE5A-cGMP-PKG signaling to mitochondrial integrity and metabolism broadened its role beyond contractility.

    Evidence Burn-injury rodent model with electron microscopy, respirometry, ETC complex assays, and sildenafil treatment; C2C12 overexpression/knockdown linking PDE5A to proteasome suppression, ER stress, and insulin resistance

    PMID:30774657 PMID:32231130

    Open questions at the time
    • Causal link rests partly on pharmacological inhibition rather than genetic loss
    • Mechanism connecting cGMP-PKG to mitochondrial respiration not resolved
  9. 2022 High

    A knockout model established PDE5A as a positive regulator of platelet activation and thrombosis by limiting intracellular cGMP.

    Evidence PDE5A-/- mice with aggregation, integrin activation, calcium/ROS, VASP/MAPK signaling assays, and in vivo FeCl3 thrombosis and bleeding-time measurements

    PMID:36252813

    Open questions at the time
    • Upstream guanylyl cyclase input in platelets not dissected
    • Relevance to human antiplatelet pharmacology not established
  10. 2022 Medium

    Direct SMAD2/3 binding to the PDE5A promoter linked myostatin signaling to PDE5A repression and downstream PKG-driven glycolysis.

    Evidence ChIP-qPCR for SMAD2/3 occupancy, transcriptome analysis, glycolysis assays, and PKG knockdown rescue in myostatin-mutant cattle hearts

    PMID:35155444

    Open questions at the time
    • Conservation of SMAD2/3 regulation in human heart not shown
    • Direct PKG-PFK phosphorylation site not mapped
  11. 2024 High

    Identifying OTUD1-mediated deubiquitination defined the first post-translational stabilization mechanism for PDE5A, with consequences for cardiac calcium handling.

    Evidence LC-MS/MS, Co-IP mapping to GAF1/PDEase domains, K48-chain ubiquitination assays via OTUD1 Cys320, and OTUD1 KO/overexpression with cardiac functional readouts

    PMID:38185350

    Open questions at the time
    • E3 ligase ubiquitinating PDE5A not identified
    • Signals controlling OTUD1-PDE5A engagement unknown
  12. 2024 Medium

    Gain-of-function studies extended PDE5A's cGMP-lowering role to striatal neurons, linking it to dendritic complexity, excitability, and behavior.

    Evidence PDE5A overexpression in primary striatal neurons and AAV-mediated striatal overexpression in mice, with tadalafil rescue and behavioral and gene-expression profiling

    PMID:39695100

    Open questions at the time
    • Endogenous neuronal PDE5A loss-of-function not tested
    • Circuit-level mechanism of behavioral effects unresolved
  13. 2025 Medium

    Genetic and microenvironmental studies revealed context-dependent and partly contradictory roles for PDE5A in metabolism, vascular protection, hypertrophy, and tumor immunosuppression.

    Evidence Pde5a KO obesity/fat-browning model with cAMP-PKA assays; RUNX1-PDE5A axis in VSMC aortic dissection; TAC hypertrophy in KO mice with cAMP/cGMP and LDH profiling; scRNA-seq/spatial transcriptomics of PDE5A+ CAFs with vardenafil/LAG3 combination

    PMID:40659490 PMID:40912399 PMID:41115748 PMID:41853865

    Open questions at the time
    • KO and pharmacological inhibition give divergent hypertrophy outcomes, complicating mechanism
    • Convergence of cGMP and cAMP-PKA signaling not mechanistically resolved
    • Direct cGMP substrate dependence of CAF immunosuppression not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single cGMP-hydrolyzing enzyme produces opposing tissue-specific outcomes—and how its localization, isoform usage, and post-translational stabilization are coordinated to direct these roles—remains unresolved.
  • No unifying model reconciling genetic vs pharmacological discrepancies in cardiac hypertrophy
  • Molecular determinants of caveolar vs z-band targeting unknown
  • Functional differences among A1/A2/A3 isoforms uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 3 GO:0016787 hydrolase activity 2
Localization
GO:0005829 cytosol 1 GO:0005856 cytoskeleton 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 2 R-HSA-109582 Hemostasis 1 R-HSA-397014 Muscle contraction 1
Partners
NOS3OTUD1PKG1

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Human PDE5A1 encodes an 875-amino-acid cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase that hydrolyzes cGMP; activity was confirmed in yeast expression system and was inhibited by selective PDE5 inhibitors zaprinast and DMPPO. A 5'-splice variant PDE5A2 encodes an 833-amino-acid protein with eight unique N-terminal amino acids. cDNA cloning, yeast expression system with enzymatic activity assay, selective inhibitor testing Gene High 9714779
1998 The human PDE5A gene contains 21 exons and its catalytic domain shares evolutionary relatedness with PDE6B; gene mapped to chromosome 4q26 by FISH. PDE5A mRNA is expressed in smooth muscle cells, megakaryocyte-like cells, and multiple tissues. Genomic cloning, exon-intron mapping, fluorescence in situ hybridization (FISH) European journal of biochemistry Medium 9716380
2000 Three PDE5A isoforms (A1, A2, A3) arise from three alternative first exons arranged in the order A1-A3-A2. An intronic promoter between the A3- and A2-specific exons drives PDE5A2 expression and is bound by transcription factors AP-2 and Sp1. RACE-PCR, genomic cloning, DNase I footprint analysis, promoter-reporter assay Biochemical and biophysical research communications Medium 10679249
2001 The PDE5A gene promoter (full basal activity confined to a 139-bp region containing the PDE5A1 first exon) contains AP2- and Sp1-binding sites identified by DNase I footprinting; both cAMP and cGMP upregulate promoter activity through 5' and 3' extensions containing these binding sites. Luciferase reporter assay, DNase I footprint analysis, deletion mapping Biochemical and biophysical research communications Medium 11162575
2002 Three PDE5A isoforms (A1, A2, A3) are expressed from two alternate promoters in human corpus cavernosum; both promoters are upregulated by increasing concentrations of cAMP or cGMP, providing a positive feedback mechanism. RACE-PCR, RT-PCR, promoter-reporter assay International journal of impotence research Medium 11896473
2008 PDE5A is expressed and enzymatically active in cardiac myocytes. shRNA-mediated PDE5A gene silencing eliminated immunoreactivity and suppressed PDE5 enzyme activity, confirming specificity. PDE5A overexpression (DsRed-PDE5 fusion) showed z-band localization in adult myocytes that became diffuse in eNOS-/- myocytes. PDE5A silencing blunted phenylephrine-induced hypertrophy in a PKG-dependent manner, equivalent to sildenafil with no additive effect. shRNA gene silencing in adenoviral vector, DsRed fusion protein imaging, PDE enzyme activity assay, immunoblot, immunofluorescence, eNOS-/- mouse cardiomyocytes Cellular signalling High 18790048
2010 PDE5A inhibition (sildenafil) suppresses acute beta-adrenergic (isoproterenol) stimulation of sarcomere shortening in cardiac myocytes without altering calcium transients. This requires beta3-adrenergic receptor coupling to NOS signaling upstream, and PKG-mediated phosphorylation of troponin I at Ser23/Ser24 downstream. Genetic deletion or pharmacological blockade of beta3-AR fully prevented sildenafil modulation. Myocytes expressing slow skeletal TnI (lacking Ser23/Ser24 sites) showed no modulation. Video microscopy (sarcomere shortening), fura2-AM calcium imaging, genetic KO mice (beta3-AR-/-), pharmacological inhibitors, non-equilibrium isoelectric focusing gel electrophoresis for TnI phosphorylation Basic research in cardiology High 20107996
2011 In melanoma cells, oncogenic BRAF acting through MEK and transcription factor BRN2 downregulates PDE5A transcription. PDE5A downregulation leads to elevated cGMP, increased cytosolic Ca2+, enhanced contractility, and invasion. This pathway operates specifically in BRAF-mutant melanoma, not in NRAS-mutant melanoma or BRAF-mutant colorectal cells. siRNA knockdown, pharmacological MEK inhibition, BRN2 knockdown, cGMP measurement, Ca2+ imaging, invasion assays, lung colonization assays Cancer cell High 21215707
2011 PDE5A is primarily localized to caveolin-rich lipid rafts/caveolae in vascular endothelial cells (human, mouse, bovine). PDE5A at caveolae creates a feedback loop with NOS3: PDE5A inhibitors increase NOS3 activity, while PDE5A overexpression (adenoviral) decreases NOS3 activity and endothelium-dependent vasodilation. PKG1 directly regulates NOS3 phosphorylation at S1179; PKG1 overexpression activates NOS3, while PKG1 siRNA inhibits NOS3 phosphorylation and activity. Subcellular fractionation (caveolin-rich lipid raft isolation), adenoviral overexpression in vitro and in vivo, siRNA knockdown of PKG1, NOS3 activity assay, endothelium-dependent vasodilation assay Cardiovascular research High 21421555
2014 Ser102 and Ser104 in PDE5A regulate its enzymatic activity and conformational state: the double mutant Ser102Ala/Ser104Ala shows approximately two-fold higher cGMP hydrolysis activity than wild-type PDE5A and migrates as a single band (vs. doublet for WT) on native acrylamide gel, suggesting these residues influence conformational flexibility and phosphorylation status. Localization was not altered by the mutations or by sildenafil, cilostazol, glyceryl trinitrate, CGRP, or sumatriptan. Site-directed mutagenesis, GFP fusion protein overexpression in SK-N-AS cells, in vitro [3H]cGMP hydrolysis assay, native PAGE, immunofluorescence PloS one Medium 25247292
2018 miR-19a/b-3p directly targets the PDE5A 3'UTR to suppress PDE5A mRNA and protein expression. miR-19a/b-3p transgenic mice were protected from Ang II-induced cardiac hypertrophy and remodeling, acting through PDE5A suppression. Luciferase reporter assay (3'UTR), transfection of miR-19a/b-3p, western blot, RT-PCR, transgenic mouse model with echocardiography and pressure-volume analysis Journal of hypertension Medium 29664809
2019 PDE5A overexpression in C2C12 myotubes suppresses proteasome activity, causing ER stress and subsequent insulin resistance (reduced Akt phosphorylation and glucose uptake). PDE5A knockdown had the opposite effects. The PDE5 inhibitor icariin restored proteasome activity and mitigated ER stress and insulin resistance caused by PDE5A overexpression. Adenoviral overexpression and shRNA knockdown, western blot for Akt phosphorylation and ER stress markers, 2-DG glucose uptake assay, proteasome activity assay International journal of endocrinology Medium 30774657
2020 Burn injury interrupts the PDE5A-cGMP-PKG pathway, leading to cardiac mitochondrial dysfunction including impaired mitochondrial morphology, reduced mtDNA-encoded gene expression, decreased State 3 oxygen consumption, reduced respiratory complex activities (I, III, IV, V), and reduced ATP and MnSOD. Sildenafil (PDE5A inhibitor) preserved mitochondrial structure, respiratory chain efficiency, and energy status. Transmission electron microscopy, real-time qPCR, O2K-respirometer, electron transport chain complex activity assays, sildenafil treatment in rodent burn model International journal of molecular sciences Medium 32231130
2022 PDE5A deficiency in mice causes impaired platelet activation, including reduced aggregation, ATP release, P-selectin expression, integrin αIIbβ3 activation, spreading, and clot retraction. PDE5A-/- platelets have elevated intracellular cGMP, increased VASP phosphorylation, reduced phosphorylation of ERK1/2, p38, JNK, and AKT, and reduced calcium mobilization and ROS production. PDE5A-deficient mice exhibit prolonged bleeding time and delayed arterial and venous thrombus formation. PDE5A knockout mice, platelet aggregation assay, flow cytometry (P-selectin, integrin activation, annexin-V), calcium imaging (Fluo-4 AM), cGMP measurement, western blot for signaling proteins, FeCl3-induced thrombosis model, microfluidic whole-blood perfusion Thrombosis and haemostasis High 36252813
2022 In cattle hearts with myostatin mutation, downregulation of PDE5A (driven by loss of SMAD2/SMAD3 binding to PDE5A promoter) activates the cGMP-PKG signaling pathway, leading to PKG-mediated phosphorylation of phosphofructokinase (PFK) and increased glycolysis. ChIP-qPCR confirmed SMAD2/SMAD3 complex binding to the PDE5A promoter. PKG knockdown reversed PFK phosphorylation and glycolysis increase. Chromatin immunoprecipitation qPCR (ChIP-qPCR), transcriptome analysis, biochemical glycolysis assays, PKG knockdown Frontiers in cell and developmental biology Medium 35155444
2024 OTUD1 deubiquitinase directly binds to the GAF1 and PDEase domains of PDE5A (by LC-MS/MS and Co-IP). OTUD1 stabilizes PDE5A by reversing K48-linked ubiquitin chains via its catalytic Cys320, preventing proteasomal degradation. Stabilized PDE5A inactivates the cGMP-PKG-SERCA2a signaling axis, disrupting calcium handling in cardiomyocytes and promoting heart failure. LC-MS/MS, Co-immunoprecipitation, ubiquitination assay, OTUD1 knockout mice and overexpression, NRVM knockdown/overexpression, cardiac functional measurements Biochimica et biophysica acta. Molecular basis of disease High 38185350
2024 miR-214 directly targets and negatively regulates PDE5A; elevated PDE5A expression in dilated cardiomyopathy reduces cGMP levels. Sildenafil (PDE5A inhibitor) reversed the cGMP reduction caused by PDE5A elevation, validating the regulatory mechanism. Bioinformatics, qRT-PCR and western blot in patient serum/samples, sildenafil treatment to confirm PDE5A-cGMP link Scientific reports Low 39543318
2024 PDE5A overexpression in mouse striatal neurons reduces cGMP levels, decreases dendrite complexity, increases apoptosis, and enhances neuronal excitability; these effects were rescued by the PDE5-specific inhibitor tadalafil. In vivo PDE5A overexpression in mouse striatum via stereotaxic AAV injection caused decreased cGMP, upregulated neuroinflammation gene expression, and bipolar disorder-like behaviors. PDE5A overexpression in primary cultured striatal neurons, tadalafil rescue, stereotaxic AAV injection in mouse striatum, cGMP measurement, behavioral assays, gene expression profiling Translational psychiatry Medium 39695100
2025 PDE5A+ cancer-associated fibroblasts in gastric cancer promote immunosuppressive tumor microenvironment via the PI3K/AKT/mTOR signaling pathway, releasing CXCL12 that engages CXCR4 to recruit CD8+ TEX+ LAG3 T cells and promote T cell exclusion. Combined LAG3 blockade and PDE5A inhibitor vardenafil enhanced immunotherapy responses in mouse models. Single-cell RNA sequencing, spatial transcriptomics, in vitro and in vivo mechanistic studies, mouse tumor models with drug combination Gut Medium 41115748
2025 Loss of Pde5a (genetic KO) prevents diet-induced obesity and promotes fat browning (enhanced brown adipose tissue activation and white adipose browning) via activation of the cAMP-PKA signaling pathway. The protective metabolic effects require early developmental Pde5a knockdown and involve convergence of cGMP and cAMP signaling cascades. Pde5a knockout mouse models, phenotypic and histological analysis, thermogenic capacity measurements, cAMP-PKA signaling assays under chow and high-fat diet Molecular metabolism Medium 40912399
2025 Exercise upregulates PDE5A expression in vascular smooth muscle cells (VSMCs) through suppression of the transcriptional repressor RUNX1, which directly represses PDE5A transcription. VSMC-specific PDE5A overexpression attenuates aortic dissection progression and preserves VSMC contractile phenotype (MYH11, CNN1, α-SMA); PDE5A inhibition abolished exercise's protective effects. RNA sequencing, human AD tissue analysis, BAPN mouse AD model with treadmill exercise, gain- and loss-of-function experiments, RUNX1 inhibition studies, VSMC-specific PDE5A overexpression Arteriosclerosis, thrombosis, and vascular biology Medium 41853865
2025 Cardiac hypertrophy in Pde5a-deficient (Pde5a-/-) mice after TAC surgery was associated with an unbalanced cAMP/cGMP ratio and a metabolic shift from oxidative to mixed oxidative-glycolytic metabolism in which lactate dehydrogenase plays a critical role. Sildenafil prevented only moderate (not severe) cardiac hypertrophy in wild-type mice. Genetic ablation of Pde5a did not protect against moderate or severe cardiac hypertrophy. Pde5a knockout and wild-type mice with transverse aortic constriction (TAC), sildenafil treatment, cardiac morpho-functional assessment, cAMP/cGMP ratio measurement, LDH activity analysis, molecular marker expression Life science alliance Medium 40659490

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A. Cancer cell 185 21215707
1998 Isolation and characterization of cDNAs encoding PDE5A, a human cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase. Gene 174 9714779
2007 PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation. American journal of physiology. Lung cellular and molecular physiology 129 17965319
1998 Expression, structure and chromosomal localization of the human cGMP-binding cGMP-specific phosphodiesterase PDE5A gene. European journal of biochemistry 100 9716380
2002 Human PDE5A gene encodes three PDE5 isoforms from two alternate promoters. International journal of impotence research 88 11896473
2010 PDE5A suppression of acute beta-adrenergic activation requires modulation of myocyte beta-3 signaling coupled to PKG-mediated troponin I phosphorylation. Basic research in cardiology 87 20107996
2008 Expression, activity, and pro-hypertrophic effects of PDE5A in cardiac myocytes. Cellular signalling 79 18790048
2022 Main active components of Si-Miao-Yong-An decoction (SMYAD) attenuate autophagy and apoptosis via the PDE5A-AKT and TLR4-NOX4 pathways in isoproterenol (ISO)-induced heart failure models. Pharmacological research 75 35026404
2012 Selective PDE5A inhibition with sildenafil rescues left ventricular dysfunction, inflammatory immune response and cardiac remodeling in angiotensin II-induced heart failure in vivo. Basic research in cardiology 63 23117837
2001 Identification and regulation of human PDE5A gene promoter. Biochemical and biophysical research communications 57 11162575
2008 Pressure-overload magnitude-dependence of the anti-hypertrophic efficacy of PDE5A inhibition. Journal of molecular and cellular cardiology 45 19159628
2011 Phosphodiesterase-5A (PDE5A) is localized to the endothelial caveolae and modulates NOS3 activity. Cardiovascular research 36 21421555
2020 Burn-Induced Cardiac Mitochondrial Dysfunction via Interruption of the PDE5A-cGMP-PKG Pathway. International journal of molecular sciences 29 32231130
2011 t(4;8)(q27;q24) in Hodgkin lymphoma cells targets phosphodiesterase PDE5A and homeobox gene ZHX2. Genes, chromosomes & cancer 29 21987443
2018 MicroRNA-19a/b-3p protect the heart from hypertension-induced pathological cardiac hypertrophy through PDE5A. Journal of hypertension 28 29664809
2000 Identification of three alternative first exons and an intronic promoter of human PDE5A gene. Biochemical and biophysical research communications 24 10679249
2015 Semi-synthetic derivatives of natural isoflavones from Maclura pomifera as a novel class of PDE-5A inhibitors. Fitoterapia 17 26136059
2019 Effect of a phosphodiesterase-5A (PDE5A) gene polymorphism on response to sildenafil therapy in canine pulmonary hypertension. Scientific reports 16 31053768
2016 Reversal of neurobehavioral social deficits in dystrophic mice using inhibitors of phosphodiesterases PDE5A and PDE9A. Translational psychiatry 16 27676442
2024 OTUD1 promotes isoprenaline- and myocardial infarction-induced heart failure by targeting PDE5A in cardiomyocytes. Biochimica et biophysica acta. Molecular basis of disease 15 38185350
2021 LncRNA HOXA-AS3 Promotes the Progression of Pulmonary Arterial Hypertension through Mediation of miR-675-3p/PDE5A Axis. Biochemical genetics 15 33687636
2019 PDE5A Suppresses Proteasome Activity Leading to Insulin Resistance in C2C12 Myotubes. International journal of endocrinology 14 30774657
2022 Isolation, bioassay and 3D-QSAR analysis of 8-isopentenyl flavonoids from Epimedium sagittatum maxim. as PDE5A inhibitors. Chinese medicine 12 36587222
2013 Identification of PDE5A:E90K: a polymorphism in the canine phosphodiesterase 5A gene affecting basal cGMP concentrations of healthy dogs. Journal of veterinary internal medicine 12 24341639
2022 Myostatin Mutation Promotes Glycolysis by Increasing Phosphorylation of Phosphofructokinase via Activation of PDE5A-cGMP-PKG in Cattle Heart. Frontiers in cell and developmental biology 11 35155444
2016 PDE5A Polymorphisms Influence on Sildenafil Treatment Success. The journal of sexual medicine 10 27235284
2022 Impaired Platelet Function and Thrombus Formation in PDE5A-Deficient Mice. Thrombosis and haemostasis 9 36252813
2023 IncRNA XIST Stimulates Papillary Thyroid Cancer Development through the miR-330-3p/PDE5A Axis. Critical reviews in eukaryotic gene expression 8 37017666
2019 Hydrogen sulfide-mediated endothelial function and the interaction with eNOS and PDE5A activity in human internal mammary arteries. The Journal of international medical research 7 31155983
2010 Phosphodiesterase-5 gene (PDE5A) polymorphisms are associated with progression of childhood IgA nephropathy. Pediatric nephrology (Berlin, Germany) 7 20563733
2025 PDE5A+ cancer-associated fibroblasts enhance immune suppression in gastric cancer. Gut 6 41115748
2022 Multiomic analysis of papillary thyroid cancers identifies BAIAP2L1-BRAF fusion and requirement of TRIM25, PDE5A and PKCδ for tumorigenesis. Molecular cancer 6 36217175
2022 LncRNA ARAP1-AS1 targets miR-516b-5p/PDE5A axis to facilitate the progression of thyroid cancer. Anti-cancer drugs 6 36730555
2019 The role of PDE5a in oocyte maturation of zebrafish. General and comparative endocrinology 6 31654676
2017 Use of the KlADH3 promoter for the quantitative production of the murine PDE5A isoforms in the yeast Kluyveromyces lactis. Microbial cell factories 6 28938916
2024 miR-30d Attenuates Pulmonary Arterial Hypertension via Targeting MTDH and PDE5A and Modulates the Beneficial Effect of Sildenafil. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 5 39206778
2024 Downregulation of miR-214 promotes dilated Cardiomyopathy Progression through PDE5A-Mediated cGMP regulation. Scientific reports 4 39543318
2023 Ent-labdane-type diterpene glycosides obtained from Rubus chingii Hu and their inhibitory effects on PDE5A activity. Fitoterapia 4 38135092
2019 Discovery of two novel hetero-tricyclic lead scaffolds as PDE5A inhibitor: virtual screening, molecular docking and pharmacophore modeling approach. Natural product research 4 31137981
2014 Role of Ser102 and Ser104 as regulators of cGMP hydrolysis by PDE5A. PloS one 4 25247292
2025 Vascular remodeling in arteriovenous fistula treated with PDE5A inhibitors. Physiological reports 3 40300852
2023 A label-free LC/MS-based enzymatic activity assay for the detection of PDE5A inhibitors. Frontiers in chemistry 3 36860644
2021 Sildenafil Citrate Downregulates PDE5A mRNA Expression in Women with Recurrent Pregnancy Loss without Altering Angiogenic Factors-A Preliminary Study. Journal of clinical medicine 3 34768607
2019 Novel Pyrazolo[4, 3-c]Quinolin-3-One Derivatives as PDE5A Inhibitors. Current topics in medicinal chemistry 3 30747070
2013 Chronic vasodilation increases renal medullary PDE5A and α-ENaC through independent renin-angiotensin-aldosterone system pathways. American journal of physiology. Regulatory, integrative and comparative physiology 3 24068049
2025 Pde5a deficiency prevents diet-induced obesity via adipose cAMP-PKA activation enhancing fat browning. Molecular metabolism 2 40912399
2023 Co-expression of soluble guanylyl cyclase subunits and PDE5A shRNA to elevate cellular cGMP level: A potential gene therapy for myocardial cell death. Technology and health care : official journal of the European Society for Engineering and Medicine 2 36442224
2023 Icariin has the potential to induce the differentiation of bone marrow mesenchymal stem cells into brown fat cells via PDE5A inhibition. Heliyon 2 38094047
2021 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) 2 34829647
2026 Exercise Attenuates Aortic Dissection Via PDE5A-Mediated Inhibition of Vascular Smooth Muscle Cell Phenotypic Switch. Arteriosclerosis, thrombosis, and vascular biology 1 41853865
2025 Icariin targets PDE5A to regulate viability, DNA synthesis and DNA damage of spermatogonial stem cells and improves reproductive capacity. Asian journal of andrology 1 39774071
2024 Hsa_circ_0092355 Accelerates Papillary Thyroid Cancer Progression by Regulating the miR-543/PDE5A Pathway. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 1 38286403
2019 Hetero-Tricyclic Lead Scaffold as Novel PDE5A Inhibitor for Antihypertensive Activity: In Silico Docking Studies. Current computer-aided drug design 1 30767749
2026 Endothelial miR-7052 Safeguards Blood-Brain Barrier Integrity During Endotoxemia by Co-repressing ANGPT2 and PDE5A. Molecular neurobiology 0 41677948
2025 The rewiring of cAMP/cGMP and LDH signalling drives cardiac hypertrophy in Pde5a mice. Life science alliance 0 40659490
2024 Exploring PDE5A upregulation in bipolar disorder: insights from single-nucleus RNA sequencing of human basal ganglia. Translational psychiatry 0 39695100

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