The antithrombotic effect of caffeic acid is associated with a cAMP-dependent pathway and clot retraction in human platelets

• Published in: Thrombosis research 2020-11, Vol.195, p.87-94
• Main Authors: Nam, Gi Suk, Park, Hwa-Jin, Nam, Kyung-Soo
• Format: Article
• Language: English
• Subjects: Caffeic acid; Clot retraction; Coagulation; Cyclic adenosine monophosphate; Platelet activation; Thrombosis
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2020.07.024

Caffeic acid (CA) is a polyphenol widely distributed in the plant kingdom. Studies have shown CA possesses antithrombotic activity in mouse cerebral arterioles in vivo and inhibits platelet aggregation in vitro. However, little is known regarding the effects of CA on platelet-mediated clot retraction. We investigated the effects of CA on platelet activation and clot retraction in response to thrombin. CA inhibited thrombin-induced platelet aggregation, calcium mobilization, adenosine 1,4,5-tri-phosphate (ATP) release, P-selectin expression and fibrinogen binding to integrin αIIbβ3 activation without inducing any cytotoxic effect, and inhibited the phosphorylations of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) in thrombin-stimulated platelets. In addition, CA enhanced cyclic adenosine monophosphate (cAMP) generation, which led to the phosphorylations of vasodilator-stimulated phosphoprotein (VASP) and inositol trisphosphate (IP3) receptor, and reduced clot retraction without any anticoagulation effect. Dipyridamole, a phosphodiesterase 3 (PDE3) inhibitor, reduced clot retraction, which suggested CA-mediated cAMP generation is the main signaling pathway responsible for its inhibition of clot retraction. Taken together, the findings of the present study suggest that CA may have potential as a therapeutic for the prevention of thrombotic disorders. •Caffeic acid (CA) inhibited thrombin-induced platelet aggregation without cytotoxicity.•CA delayed the kinetics of clot retraction and inhibited fibrinogen binding to integrin αIIbβ3.•CA-mediated antiplatelet effect was associated with cAMP-dependent pathway.