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Updated: Oct 22, 2025
Microfluidics in Assessing Platelet Function
Published on: November 8, 2024
Inhibition of Phosphodiesterase 3A by Cilostazol Dampens Proinflammatory Platelet Functions
Daniëlle M Coenen1,2, Alexandra C A Heinzmann1, Silvia Oggero3
1Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands.
Insights
Phosphodiesterase (PDE) 3 and 5 inhibitors impact platelet inflammatory functions. Cilostazol (PDE3A inhibitor) reduced platelet procoagulant activity and inflammatory mediator release, while tadalafil (PDE5 inhibitor) showed some anti-inflammatory effects.
Area of Science:
- * Cardiovascular Research
- * Platelet Biology
- * Thromboinflammation
Background:
- * Platelets have both hemostatic and inflammatory roles, contributing to thromboinflammatory diseases like heart attack and stroke.
- * Phosphodiesterase (PDE) inhibitors (PDE3 and PDE5) are used for secondary prevention of arterial thrombosis.
- * The impact of these inhibitors on platelet inflammatory functions remains unclear.
Purpose of the Study:
- * To investigate the effects of the PDE3A inhibitor cilostazol and the PDE5 inhibitor tadalafil on platelet function in thromboinflammation.
- * To elucidate the specific roles of PDE3A and PDE5 in platelet-mediated inflammatory responses.
Main Methods:
- * Ex vivo assessment of platelet-dependent fibrin formation under arterial flow conditions.
- * Analysis of extracellular vesicle (EV) release, specifically phosphatidylserine-positive EVs.
- * In vitro studies of platelet-endothelium and platelet-monocyte interactions.
- * Experiments using blood from Pde3a-deficient mice.
Main Results:
- * Cilostazol, but not tadalafil, delayed ex vivo platelet-dependent fibrin formation, mediated via PDE3A.
- * Cilostazol specifically reduced the release of phosphatidylserine-positive extracellular vesicles from platelets.
- * Both cilostazol and tadalafil reduced platelet interaction with inflamed endothelium and chemokine release (CCL5, CXCL4).
- * Cilostazol inhibited monocyte recruitment and platelet-monocyte interactions in vitro.
Conclusions:
- * Platelet PDE3A and PDE5 play significant roles in platelet procoagulant and proinflammatory responses.
- * Cilostazol demonstrates potent anti-inflammatory effects on platelets via PDE3A inhibition.
- * Tadalafil exhibits some anti-inflammatory effects on platelet-endothelial and platelet-monocyte interactions.
Objective:
platelets possess not only haemostatic but also inflammatory properties, which combined are thought to play a detrimental role in thromboinflammatory diseases such as acute coronary syndromes and stroke. Phosphodiesterase (PDE) 3 and -5 inhibitors have demonstrated efficacy in secondary prevention of arterial thrombosis, partially mediated by their antiplatelet action. Yet it is unclear whether such inhibitors also affect platelets' inflammatory functions. Here, we aimed to examine the effect of the PDE3A inhibitor cilostazol and the PDE5 inhibitor tadalafil on platelet function in various aspects of thromboinflammation. Approach and results: cilostazol, but not tadalafil, delayed ex vivo platelet-dependent fibrin formation under whole blood flow over type I collagen at 1000 s-1. Similar results were obtained with blood from Pde3a deficient mice, indicating that cilostazol effects are mediated via PDE3A. Interestingly, cilostazol specifically reduced the release of phosphatidylserine-positive extracellular vesicles (EVs) from human platelets while not affecting total EV release. Both cilostazol and tadalafil reduced the interaction of human platelets with inflamed endothelium under arterial flow and the release of the chemokines CCL5 and CXCL4 from platelets. Moreover, cilostazol, but not tadalafil, reduced monocyte recruitment and platelet-monocyte interaction in vitro.
Conclusions:
this study demonstrated yet unrecognised roles for platelet PDE3A and platelet PDE5 in platelet procoagulant and proinflammatory responses.
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