Related Experiment Video
Updated: Jan 11, 2026
Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets
Published on: May 11, 2015
Cyclic Nucleotide Phosphodiesterase Families as Targets to Treat Pulmonary Arterial Hypertension: Beyond PDE5
Liting Wang1,2, Rodolphe Fischmeister1, Boris Manoury1
1Université Paris-Saclay, Inserm, UMR-S 1180, 91400 Orsay, France.
Insights
Pulmonary arterial hypertension (PAH) therapies targeting cyclic nucleotide pathways are limited. Investigating other phosphodiesterase (PDE) inhibitors may offer new treatment options for this fatal disease.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Molecular Biology
Background:
- Pulmonary arterial hypertension (PAH) is a severe, incurable disease.
- Current PAH therapies primarily target cyclic nucleotide pathways (cAMP and cGMP).
- Phosphodiesterases (PDEs) degrade cyclic nucleotides; PDE5 inhibitors are currently approved for PAH.
Purpose of the Study:
- To review research on inhibiting various phosphodiesterase (PDE) families for PAH treatment.
- To explore alternative therapeutic strategies beyond PDE5 inhibition.
- To synthesize evidence on PDE isoform expression and drug efficacy in PAH.
Main Methods:
- Review of in vivo and ex vivo studies.
- Analysis of biological samples from PAH patients.
- Examination of pharmacological compounds targeting PDE isoforms.
Main Results:
- Evidence for PDE isoform expression in lung vasculature.
- Assessment of efficacy and limitations of various PDE inhibitors.
- Identification of pathological processes targeted by PDE inhibition.
Conclusions:
- PDE inhibition beyond PDE5 holds therapeutic potential for PAH.
- Further research into specific PDE isoforms is warranted.
- Targeting PDE pathways offers promising avenues for novel PAH treatments.
Abstract:
Pulmonary arterial hypertension (PAH) is a fatal disease with no cure. Until recently, most specific therapies for PAH had aimed at enhancing cyclic nucleotide (cAMP and cGMP) pathways, taking advantage of the vasorelaxant and antiproliferative properties of these key intracellular messengers. This process can be achieved by inhibiting phosphodiesterases (PDEs), which are intracellular enzymes responsible for cyclic nucleotide degradation. To date, only inhibitors of PDE type 5 (PDE5) have been approved for the treatment of PAH. Because the PDE superfamily comprises 11 families that encompass many variants, substantial experimental investigation has been conducted to assess the relevance of inhibiting other PDE families, aiming to offer therapeutic alternatives. This review synthesizes the main research work conducted on in vivo or ex vivo models, as well as on biological resources from patients. It helps provide evidence for the expression of PDE isoforms in the lung vasculature, as well as the efficacy and limitations of various pharmacological compounds tested for inhibiting pathological processes ongoing in the disease. Perspectives and suggestions for future research orientation are proposed.
Related Concept Videos
01:28Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors
Among the PDE5 inhibitors, sildenafil (Revatio) stands out as a competitive and selective inhibitor. It operates by elevating cellular levels of cGMP and augmenting signaling through the cGMP-PKG pathway, promoting vasodilation. Upon oral...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
01:30Pulmonary Hypertension: Classification and Pathogenesis
There are various classifications for PH, each relating to different underlying causes and also...