ReviewJournal of thrombosis and haemostasis : JTH2022
The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders.
Review in Journal of thrombosis and haemostasis : JTH, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Trends and mechanistic insights into hypertension-associated hearing loss: a 20-year perspective (2005-2025).Frontiers in molecular neuroscience · 2026Pooled it
- Platelet Drp1 phosphorylation provides a platform for immune-based platelet function testing.Blood · 2026Article
- Targeting canonical TGFβ/SMAD3 and ERK1/2 signaling in human valve interstitial cells to modulate immune-fibrotic responses in rheumatic heart disease.Journal of physiology and biochemistry · 2026Article
- The Role of Platelets in Pulmonary Hypertension: From Activation to Pulmonary Vascular Remodeling-A Review Article.Biomedicines · 2026Review
- Treatment with Sildenafil Promotes Angiogenesis and Modulates Immune Response in Ischemic Muscle Tissue.Current issues in molecular biology · 2026Article
- Mechanism of traditional Chinese medicine in treating erectile dysfunction: A review.Medicine · 2026Review
- Clinical Application of Inhaled Nitric Oxide in Conditions of Excessive Right Heart Load: A Review from Neonatal Pulmonary Hypertension to Perioperative Cardiac Surgery Management.Journal of cardiovascular development and disease · 2026Review
- Recent advances in drug repositioning and rediscovery for different therapeutic activities utilizing updated technological approaches.Molecular diversity · 2026Review
- Nitric Oxide Signaling in Cardiovascular Physiology and Pathology: Mechanisms, Dysregulation, and Therapeutic Frontiers.International journal of molecular sciences · 2026Review
- Lead exposure increases the risk of retinal vein occlusion: a population-based analysis and investigation of PRICKLE4/PLCXD1-mediated endothelial cell mechanisms.Frontiers in public health · 2026Article
- Platelet mitochondria dysfunction in diabetes mellitus: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- Nitric oxide: a gas transmitter in healthy and diseased skin.Medical gas research · 2025Review
- Recent advances in Pyrazolo[3,4-d]pyrimidine-based dual inhibitors in the treatment of cancers.Molecular diversity · 2025Review
- Atherosclerosis-induced arterial erectile dysfunction: pathogenesis, diagnosis, and therapeutic strategies.Translational andrology and urology · 2025Review
- Effect of phosphodiesterase inhibitors on platelet function.Biochemistry and biophysics reports · 2025Article
- Targeted codelivery of nitric oxide and hydrogen sulfide for enhanced antithrombosis efficacy.Bioactive materials · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Recent advances in the role of gasotransmitters in necroptosis.Apoptosis : an international journal on programmed cell death · 2025Review
- Potential beneficial impacts of tadalafil on cardiovascular diseases.Journal of the Chinese Medical Association : JCMA · 2025Review
- Unbiased high-throughput screening of drug-repurposing libraries identifies small-molecule inhibitors of clot retraction.Blood advances · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Platelets are the "guardians" of the blood circulatory system. At sites of vessel injury, they ensure hemostasis and promote immunity and vessel repair. However, their uncontrolled activation is one of the main drivers of thrombosis. To keep circulating platelets in a quiescent state, the endothelium releases platelet antagonists including nitric oxide (NO) that acts by stimulating the intracellular receptor guanylyl cyclase (GC). The latter produces the second messenger cyclic guanosine-3',5'-monophosphate (cGMP) that inhibits platelet activation by stimulating protein kinase G, which phosphorylates hundreds of intracellular targets. Intracellular cGMP pools are tightly regulated by a fine balance between GC and phosphodiesterases (PDEs) that are responsible for the hydrolysis of cyclic nucleotides. Phosphodiesterase type 5 (PDE5) is a cGMP-specific PDE, broadly expressed in most tissues in humans and rodents. In clinical practice, PDE5 inhibitors (PDE5i) are used as first-line therapy for erectile dysfunction, pulmonary artery hypertension, and lower urinary tract symptoms. However, several studies have shown that PDE5i may ameliorate the outcome of various other conditions, like heart failure and stroke. Interestingly, NO donors and cGMP analogs increase the capacity of anti-platelet drugs targeting the purinergic receptor type Y, subtype 12 (P2Y12) receptor to block platelet aggregation, and preclinical studies have shown that PDE5i inhibits platelet functions. This review summarizes the molecular mechanisms underlying the effect of PDE5i on platelet activation and aggregation focusing on the therapeutic potential of PDE5i in platelet disorders, and the outcomes of a combined therapy with PDE5i and NO donors to inhibit platelet activation.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.