Affinage

PDE5A

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

Length
875 aa
Mass
100.0 kDa
Annotated
2026-04-29
56 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PDE5A is a cGMP-binding, cGMP-specific 3',5'-cyclic nucleotide phosphodiesterase that hydrolyzes cGMP to GMP, thereby controlling intracellular cGMP levels and downstream PKG signaling across diverse tissues including vascular smooth muscle, cardiomyocytes, platelets, adipose tissue, and neurons (PMID:9714779, PMID:20107996, PMID:36252813, PMID:40912399, PMID:39695100). Three isoforms (PDE5A1, PDE5A2, PDE5A3) are generated from alternative promoters containing Sp1 and AP-2 elements that mediate cAMP/cGMP-dependent transcriptional feedback, while additional transcriptional regulation occurs through BRAF-MEK-BRN2 repression in melanoma and RUNX1 repression in vascular smooth muscle, and post-transcriptional control involves miR-19a/b-3p targeting of the 3'UTR (PMID:11896473, PMID:21215707, PMID:41853865, PMID:29664809). Protein stability is regulated by OTUD1-mediated removal of K48-linked ubiquitin chains that protect PDE5A from proteasomal degradation, and phosphorylation at Ser102/Ser104 modulates conformational flexibility and catalytic activity (PMID:38185350, PMID:25247292). In cardiomyocytes PDE5A localizes to z-bands in an eNOS-dependent manner and modulates contractility via PKG-dependent troponin I phosphorylation, while in platelets PDE5A loss elevates cGMP-VASP signaling to impair aggregation and thrombus formation, and in adipose tissue PDE5A deficiency activates cAMP-PKA–driven thermogenesis conferring resistance to diet-induced obesity (PMID:18790048, PMID:20107996, PMID:36252813, PMID:40912399).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1998 High

    Establishing the molecular identity and enzymatic specificity of PDE5A resolved that human PDE5A1 encodes an 875-amino-acid cGMP-specific phosphodiesterase inhibitable by zaprinast and DMPPO, and that the gene maps to 4q26 with 21 exons sharing structural homology with PDE6B.

    Evidence Heterologous expression in yeast with enzymatic assay and pharmacological inhibition; genomic sequencing and FISH mapping

    PMID:9714779 PMID:9716380

    Open questions at the time
    • No crystal structure of full-length human PDE5A determined in these studies
    • Substrate kinetics for different isoforms not compared
  2. 2002 High

    Defining the promoter architecture and isoform regulation revealed that three PDE5A isoforms arise from two alternative promoters with Sp1/AP-2 elements mediating cAMP/cGMP-dependent transcriptional upregulation, establishing a cyclic nucleotide feedback loop at the transcriptional level.

    Evidence RACE-PCR, luciferase reporter assays, DNase I footprinting, and deletion mapping across multiple studies

    PMID:10679249 PMID:11162575 PMID:11896473

    Open questions at the time
    • Identity of kinases or phosphatases mediating the cAMP/cGMP signal to Sp1/AP-2 not defined
    • Relative physiological contribution of each promoter in specific tissues unknown
  3. 2008 High

    Demonstrating that PDE5A is expressed and active in cardiomyocytes with eNOS-dependent z-band localization, and that its inhibition suppresses hypertrophy via PKG, established PDE5A as a spatially compartmentalized cardiac signaling node rather than solely a vascular smooth muscle enzyme.

    Evidence shRNA knockdown, DsRed-PDE5 fusion imaging, eNOS knockout mice, enzyme activity assay, video microscopy of sarcomere shortening

    PMID:18790048 PMID:19159628

    Open questions at the time
    • Mechanism anchoring PDE5A to z-bands not identified
    • Whether cardiac PDE5A isoform expression differs from vascular tissues not resolved
  4. 2010 High

    Mapping the full signaling cascade from PDE5A inhibition through β3-adrenergic receptor/NOS/cGMP/PKG to troponin I Ser23/24 phosphorylation defined the complete molecular pathway by which PDE5A controls cardiac contractility, ruling out PDE2/PDE3 cross-talk.

    Evidence β3-AR knockout mice, pharmacological inhibitors, sarcomere shortening video microscopy, Fura-2 Ca²⁺ imaging, TnI phosphorylation gel electrophoresis

    PMID:20107996

    Open questions at the time
    • Whether this pathway operates identically in human cardiomyocytes not demonstrated
    • Role of PDE5A in diastolic function not addressed
  5. 2011 High

    Two discoveries expanded PDE5A's regulatory context: in endothelial cells PDE5A localizes to caveolae and engages a PKG1-NOS3 feedback loop, while in melanoma BRAF-MEK-BRN2 transcriptionally represses PDE5A to elevate cGMP-Ca²⁺ signaling and drive invasion.

    Evidence Caveolar fractionation with adenoviral overexpression/siRNA and vasodilation assays; genetic epistasis with BRAF/MEK/BRN2, cGMP/Ca²⁺ imaging, mouse colonization model

    PMID:21215707 PMID:21421555

    Open questions at the time
    • Direct BRN2 binding site on PDE5A promoter not mapped
    • Whether caveolar localization requires direct caveolin binding not established
  6. 2014 Medium

    Mutagenesis of Ser102/Ser104 showed these residues control PDE5A conformational flexibility and catalytic activity, with the double alanine mutant exhibiting ~2-fold higher cGMP hydrolysis, revealing an allosteric regulatory site distinct from the catalytic pocket.

    Evidence Site-directed mutagenesis, [³H]cGMP hydrolysis assay, native PAGE

    PMID:25247292

    Open questions at the time
    • Identity of the kinase(s) phosphorylating Ser102/Ser104 in vivo not determined
    • Structural basis of conformational change not resolved
    • Single lab, no independent replication
  7. 2018 High

    Identification of miR-19a/b-3p as a direct post-transcriptional repressor of PDE5A via its 3'UTR, with transgenic mice protected from cardiac hypertrophy, established microRNA control as a disease-relevant layer of PDE5A regulation.

    Evidence Luciferase 3'UTR reporter assay, miRNA transgenic mice, echocardiography, pressure-volume analysis

    PMID:29664809

    Open questions at the time
    • Whether other miRNAs cooperate to regulate PDE5A in the heart not explored
    • Relative contribution of miR-19a vs miR-19b not distinguished
  8. 2022 High

    PDE5A knockout platelets revealed that PDE5A is essential for normal platelet activation, demonstrating that loss of PDE5A elevates cGMP-VASP signaling and broadly impairs aggregation, secretion, integrin activation, and thrombus formation in vivo.

    Evidence PDE5A knockout mice, platelet aggregation, flow cytometry, Fluo-4 AM Ca²⁺ mobilization, FeCl₃ thrombosis model, microfluidic perfusion

    PMID:36252813

    Open questions at the time
    • Whether PDE5A-deficient platelets have altered bleeding times not reported
    • Contribution of individual PDE5A isoforms in platelets unknown
  9. 2024 High

    Discovery that OTUD1 deubiquitinates PDE5A by removing K48-linked ubiquitin chains through Cys320, preventing proteasomal degradation and thereby inactivating cGMP-PKG-SERCA2a signaling, identified a direct post-translational mechanism controlling PDE5A protein stability in cardiomyocytes and heart failure.

    Evidence LC-MS/MS, Co-IP with domain mapping (GAF1 and PDEase domains), ubiquitination assays with catalytic-dead mutant, NRVM knockdown/overexpression, calcium handling measurements

    PMID:38185350

    Open questions at the time
    • E3 ubiquitin ligase targeting PDE5A for degradation not identified
    • Whether OTUD1-PDE5A interaction is regulated by upstream signals unknown
  10. 2025 High

    Multiple 2025 studies expanded PDE5A's systemic roles: adipose-specific Pde5a deficiency activated cAMP-PKA thermogenesis conferring obesity resistance; striatal PDE5A overexpression reduced dendritic complexity and increased neuronal excitability; RUNX1 was identified as a transcriptional repressor of PDE5A in VSMCs mediating exercise-protective effects; and Pde5a loss altered cardiac metabolic programming under pressure overload.

    Evidence Pde5a KO mice with metabolic phenotyping and cAMP/PKA assays; stereotaxic viral overexpression with electrophysiology and behavioral testing; VSMC-specific gain/loss-of-function in aortic dissection models; KO mice with TAC and metabolic readouts

    PMID:39695100 PMID:40659490 PMID:40912399 PMID:41853865

    Open questions at the time
    • Whether cGMP-to-cAMP crosstalk in adipose tissue involves specific PDE isoform interactions not defined
    • Mechanism linking PDE5A to neuroinflammation gene expression in striatum not resolved
    • Direct RUNX1 binding to PDE5A promoter requires ChIP-seq confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the identity of the E3 ubiquitin ligase that targets PDE5A for degradation, the structural basis of Ser102/104-dependent allosteric regulation, the mechanism anchoring PDE5A to z-bands, and how PDE5A coordinates cGMP and cAMP compartmentalization across different cell types.
  • No full-length human PDE5A structure with regulatory domains resolved
  • E3 ligase for PDE5A unknown
  • Mechanism of z-band and caveolar targeting undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 3 GO:0140657 ATP-dependent activity 1
Localization
GO:0005829 cytosol 2 GO:0005856 cytoskeleton 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1430728 Metabolism 2 R-HSA-109582 Hemostasis 1 R-HSA-392499 Metabolism of proteins 1
Partners
BRN2NOS3OTUD1PKG1RUNX1

Evidence

Reading pass · 24 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; this activity is inhibited by selective PDE5 inhibitors zaprinast and DMPPO, as demonstrated by expression in yeast and enzymatic assay. Heterologous expression in yeast, in vitro enzymatic assay, pharmacological inhibition Gene High 9714779
1998 The human PDE5A gene contains 21 exons and maps to chromosome 4q26; its catalytic domain shows evolutionary relatedness to the rod photoreceptor phosphodiesterase beta-subunit (PDE6B) gene based on exon-intron organization comparison. Genomic library isolation, FISH chromosomal mapping, genomic structure analysis European journal of biochemistry High 9716380
2002 The human PDE5A gene encodes three isoforms (PDE5A1, PDE5A2, PDE5A3) from two alternative promoters; the upstream promoter drives all three isoforms while an intronic promoter drives only PDE5A2. Both promoters are upregulated by cAMP and cGMP, with AP2 and Sp1 binding sites identified as mediators. RACE-PCR, RT-PCR, promoter cloning, luciferase reporter assay, DNase I footprint analysis International journal of impotence research High 11896473
2001 A 139-bp region containing the PDE5A1-specific first exon constitutes the core basal promoter; Sp1 and AP2 binding sites in flanking sequences mediate cAMP/cGMP-dependent transcriptional upregulation of PDE5A. Luciferase reporter assay, DNase I footprint analysis, deletion mapping Biochemical and biophysical research communications High 11162575
2000 Three alternative first exons for PDE5A isoforms are arranged in order A1-A3-A2; the intron between the A3- and A2-specific exons has promoter activity bound by transcription factors AP-2 and Sp1, while the intron between A1- and A3-specific exons lacks promoter activity. RACE-PCR, promoter activity assays, DNase I footprint analysis Biochemical and biophysical research communications High 10679249
2011 In melanoma cells, oncogenic BRAF acting through MEK and the transcription factor BRN2 transcriptionally downregulates PDE5A, causing increased cGMP, elevated cytosolic Ca2+, increased actomyosin contractility, and stimulation of cell invasion and lung colonization. Genetic epistasis (BRAF/MEK/BRN2 manipulation), siRNA knockdown, cGMP measurement, Ca2+ imaging, invasion assays, mouse colonization model Cancer cell High 21215707
2010 PDE5A inhibition (sildenafil) suppresses beta-adrenergic receptor-stimulated cardiac contractility through a cascade requiring beta3-adrenergic receptor stimulation, NOS-NO-cGMP synthesis, PKG activation, and PKG-dependent phosphorylation of troponin I at Ser23/Ser24; this modulation does not involve cGMP cross-talk with PDE2 or PDE3. Genetic knockout mice (beta3-AR KO), pharmacological inhibitors, video microscopy (sarcomere shortening), Fura-2 Ca2+ imaging, non-equilibrium isoelectric focusing gel electrophoresis for TnI phosphorylation Basic research in cardiology High 20107996
2008 PDE5 is expressed and enzymatically active in cardiac myocytes, localizes to z-bands in an eNOS-dependent manner (DsRed-PDE5 fusion protein is diffuse in eNOS-/- myocytes), and its inhibition or gene silencing (shRNA) suppresses phenylephrine-induced hypertrophy through a PKG-dependent mechanism. shRNA gene silencing (miRNA-155 cassette), DsRed-PDE5 fusion protein expression, immunofluorescence, enzyme activity assay, video microscopy, genetic knockout (eNOS-/-) Cellular signalling High 18790048
2011 PDE5A localizes to caveolae in vascular endothelial cells; PDE5A inhibitors increase NOS3 activity, while adenoviral PDE5A overexpression decreases NOS3 activity and PKG1 activity. PKG1 directly regulates NOS3 phosphorylation at S1179, establishing a cGMP-dependent feedback loop between endothelial PDE5A and NOS3. Subcellular fractionation to caveolin-rich lipid rafts, adenoviral overexpression in vitro and in vivo, siRNA knockdown of PKG1, NOS3 activity assays, vasodilation measurements Cardiovascular research High 21421555
2008 The anti-hypertrophic efficacy of PDE5A inhibition is magnitude-dependent on pressure-overload stress: sildenafil is ineffective against modest hypertrophy (low stress) but effective at higher stress levels where pathologic signaling (calcineurin, ERK-MAPK) is activated and suppressible by cGK-1, while modest hypertrophy is associated with enhanced GSK3beta/Akt phosphorylation that sildenafil further promotes. Transverse aortic constriction (TAC) mouse model at two severity levels, oral sildenafil, LV mass measurement, signaling kinase activity assays (calcineurin, ERK, GSK3beta, Akt), cGK-1 activity assay Journal of molecular and cellular cardiology High 19159628
2014 Ser102 and Ser104 in PDE5A regulate its conformational flexibility and enzymatic activity; the double Ser102Ala/Ser104Ala mutant shows approximately two-fold higher cGMP hydrolysis activity than wild-type and migrates as a single band on native gels (vs. doublet for WT), indicating these serines influence phosphorylation status and allosteric regulation. Site-directed mutagenesis, in vitro cGMP hydrolysis assay with [3H]cGMP, native PAGE, GFP fusion protein expression in neuroblastoma cells, immunofluorescence PloS one Medium 25247292
2018 miR-19a/b-3p directly targets PDE5A mRNA at its 3'UTR to suppress PDE5A expression; reduced miR-19a/b-3p levels in pressure-overload hypertrophic hearts lead to increased PDE5A and cardiac remodeling, while miR-19a/b-3p transgenic mice are protected from angiotensin II-induced cardiac hypertrophy. Luciferase reporter assay, miRNA transfection, RT-PCR, western blot, transgenic mouse model, echocardiography, pressure-volume analysis Journal of hypertension High 29664809
2024 The deubiquitinase OTUD1 binds directly to the GAF1 and PDEase domains of PDE5A (by Co-IP and LC-MS/MS) and removes K48-linked ubiquitin chains from PDE5A through its catalytic cysteine at position 320, thereby preventing PDE5A proteasomal degradation. Stabilized PDE5A inactivates the cGMP-PKG-SERCA2a signaling axis, dysregulating calcium handling in cardiomyocytes and promoting heart failure. LC-MS/MS, Co-immunoprecipitation, domain mapping, ubiquitination assays, NRVM knockdown/overexpression, calcium handling measurements Biochimica et biophysica acta. Molecular basis of disease High 38185350
2022 PDE5A deficiency in platelets elevates intracellular cGMP and VASP phosphorylation, and impairs platelet aggregation, ATP release, P-selectin expression, integrin alphaIIbbeta3 activation, spreading, clot retraction, phosphatidylserine exposure, calcium mobilization, and ROS production, resulting in delayed arterial and venous thrombus formation in vivo. PDE5A knockout mice, platelet aggregation assays, flow cytometry, calcium mobilization (Fluo-4 AM), western blot (VASP, ERK, AKT phosphorylation), FeCl3-induced thrombosis model, microfluidic perfusion assay Thrombosis and haemostasis High 36252813
2017 Murine PDE5A isoforms A1, A2, and A3 were produced in Kluyveromyces lactis with Km, Vmax, and sildenafil inhibition kinetic constants similar to native murine enzymes, confirming that the regulatory and catalytic domains of PDE5A function properly in heterologous eukaryotic expression. Heterologous protein expression, in vitro enzymatic kinetic assay (Km, Vmax), inhibitor (sildenafil) IC50 determination Microbial cell factories Medium 28938916
2019 PDE5A overexpression in C2C12 myotubes suppresses proteasome activity, leading to ER stress and subsequent insulin resistance (reduced Akt phosphorylation and glucose uptake); PDE5A knockdown has the opposite effect. PDE5 inhibition by icariin restores proteasome activity, reduces ER stress, and rescues insulin signaling. Adenoviral overexpression/knockdown, western blot (Akt phosphorylation), 2-DG glucose uptake assay, proteasome activity assay, ER stress markers International journal of endocrinology Medium 30774657
2019 In zebrafish, PDE5ab (ortholog of mammalian PDE5A) is expressed in oocytes and becomes phosphorylated during human chorionic gonadotropin-induced oocyte maturation; PDE5A inhibitors (sildenafil, tadalafil) stimulate oocyte maturation through a PKG-dependent and gap junction-dependent mechanism. In situ hybridization, western blot with phospho-specific antibody, pharmacological inhibition (sildenafil, tadalafil, KT5823 PKG inhibitor, gap junction blockers), oocyte maturation assay General and comparative endocrinology Medium 31654676
2025 Pde5a deficiency in mice activates the cAMP-PKA signaling pathway in adipose tissue, promotes brown adipose tissue activation and white adipose tissue browning, reduces hepatic lipid accumulation, and confers resistance to diet-induced obesity with improved glucose metabolism; this indicates PDE5A regulates energy homeostasis through convergence of cGMP and cAMP signaling. Pde5a knockout mouse models, high-fat diet challenge, histological analysis, metabolic phenotyping, thermogenesis measurements, cAMP/cGMP measurement, PKA activity assay Molecular metabolism High 40912399
2024 PDE5A overexpression in striatal neurons decreases cGMP levels, reduces dendritic complexity, increases apoptosis, and enhances neuronal excitability; these effects are rescued by the PDE5 inhibitor tadalafil. In vivo stereotaxic overexpression in mouse striatum upregulates neuroinflammation gene expression and induces bipolar disorder-like behaviors. Overexpression in primary cultured striatal neurons, stereotaxic viral injection in mouse striatum, cGMP measurement, morphological analysis, electrophysiology, behavioral testing, snRNA-seq validation in human brain Translational psychiatry High 39695100
2025 The transcription factor RUNX1 acts as a transcriptional repressor of PDE5A in vascular smooth muscle cells; exercise reduces RUNX1 expression, upregulates PDE5A, maintains VSMC contractile phenotype, and attenuates aortic dissection. VSMC-specific PDE5A overexpression recapitulates these protective effects, while PDE5A inhibition abolishes exercise benefit. RNA sequencing, gain/loss-of-function experiments (VSMC-specific overexpression), VSMC phenotype marker analysis, beta-aminopropionitrile AD mouse model, treadmill exercise intervention, chromatin immunoprecipitation (implied by transcriptional repressor identification) Arteriosclerosis, thrombosis, and vascular biology Medium 41853865
2025 In Pde5a-deficient mice, loss of PDE5A results in unbalanced cAMP/cGMP ratio and metabolic reprogramming toward mixed oxidative-glycolytic metabolism under pressure overload (TAC), demonstrating that PDE5A modulates cyclic nucleotide homeostasis that controls cardiac metabolic state; pharmacological sildenafil prevents moderate but not severe TAC-induced hypertrophy in wild-type mice. Pde5a knockout mice, transverse aortic constriction, echocardiography, cAMP/cGMP measurement, lactate dehydrogenase assays, molecular marker expression, sildenafil treatment Life science alliance Medium 40659490
2025 PDE5A+ cancer-associated fibroblasts promote gastric cancer immune suppression by activating the PI3K/AKT/mTOR signaling pathway and releasing CXCL12, which engages CXCR4 on CD8+ TEX+ LAG3 T cells to recruit them and facilitate immunosuppressive tumor microenvironment; combined LAG3 blockade and PDE5A inhibitor (vardenafil) enhanced immunotherapy responses in mouse models. Single-cell RNA sequencing, spatial transcriptomics, in vitro/in vivo mechanistic studies, pathway inhibition, combination therapy in mouse models Gut Medium 41115748
2013 Chronic vasodilation increases renal medullary PDE5A protein abundance through an AT1 receptor (angiotensin type 1)-dependent mechanism, as blockade of AT1 receptors (losartan) or ACE (enalapril) prevents the PDE5A upregulation, while mineralocorticoid receptor blockade (spironolactone) does not. Pharmacological intervention in rats (nifedipine, losartan, enalapril, spironolactone), western blot for renal medullary PDE5A protein American journal of physiology. Regulatory, integrative and comparative physiology Medium 24068049
2020 Burn injury disrupts the PDE5A-cGMP-PKG signaling pathway in cardiac tissue, causing mitochondrial morphological damage, reduced mitochondrial number/area, decreased mitochondrial complex I/III/IV activity (but not complex II), reduced state 3 oxygen consumption, and decreased ATP and MnSOD activity. Sildenafil (PDE5A inhibitor) preserves mitochondrial structure and respiratory chain efficiency. Rat burn model, transmission electron microscopy, real-time qPCR (mitDNA genes), O2K-respirometry, electron transport chain activity assays, ATP measurement, sildenafil treatment International journal of molecular sciences Medium 32231130

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 184 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 128 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 78 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 73 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 35 21421555
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
2020 Burn-Induced Cardiac Mitochondrial Dysfunction via Interruption of the PDE5A-cGMP-PKG Pathway. International journal of molecular sciences 24 32231130
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
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 Effect of a phosphodiesterase-5A (PDE5A) gene polymorphism on response to sildenafil therapy in canine pulmonary hypertension. Scientific reports 15 31053768
2019 PDE5A Suppresses Proteasome Activity Leading to Insulin Resistance in C2C12 Myotubes. International journal of endocrinology 13 30774657
2022 Isolation, bioassay and 3D-QSAR analysis of 8-isopentenyl flavonoids from Epimedium sagittatum maxim. as PDE5A inhibitors. Chinese medicine 12 36587222
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
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 11 24341639
2022 Impaired Platelet Function and Thrombus Formation in PDE5A-Deficient Mice. Thrombosis and haemostasis 9 36252813
2016 PDE5A Polymorphisms Influence on Sildenafil Treatment Success. The journal of sexual medicine 9 27235284
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
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
2022 Multiomic analysis of papillary thyroid cancers identifies BAIAP2L1-BRAF fusion and requirement of TRIM25, PDE5A and PKCδ for tumorigenesis. Molecular cancer 5 36217175
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 Icariin targets PDE5A to regulate viability, DNA synthesis and DNA damage of spermatogonial stem cells and improves reproductive capacity. Asian journal of andrology 2 39774071
2025 Pde5a deficiency prevents diet-induced obesity via adipose cAMP-PKA activation enhancing fat browning. Molecular metabolism 2 40912399
2025 PDE5A+ cancer-associated fibroblasts enhance immune suppression in gastric cancer. Gut 2 41115748
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
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
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
2023 Icariin has the potential to induce the differentiation of bone marrow mesenchymal stem cells into brown fat cells via PDE5A inhibition. Heliyon 1 38094047
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
2026 Exercise Attenuates Aortic Dissection Via PDE5A-Mediated Inhibition of Vascular Smooth Muscle Cell Phenotypic Switch. Arteriosclerosis, thrombosis, and vascular biology 0 41853865
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