Decreasing phosphodiesterase 5A activity contributes to platelet cGMP accumulation during storage of apheresis‐derived platelet concentrates

Abstract

Storage of APCs leads to intracellular cGMP accumulation that could be caused by degradation of PDE5A. Enhanced cGMP level supports subsequent cGMP-dependent protein kinase-mediated increase of VASP phosphorylation resulting in reduced fibrinogen binding and aggregation.

Increasing susceptibility of nitric oxide–mediated inhibitory platelet signaling during storage of apheresis‐derived platelet concentrates

“…There were no changes of basal cAMP concentrations under storage as described previously . After stimulation with DEA/NO, cAMP levels increased only weakly, up to a maximum of approximately twofold with 5 nmol/L DEA/NO (data not shown).…”

“…According to previous data basal PLT cGMP levels increased during storage, by almost 60% in APCs on Day 5 compared to Day 0. Both investigated DEA/NO concentrations (2 and 5 nmol/L) induced a significant increase of the cGMP content in PLTs from WB and stored APCs compared to unstimulated controls (Fig.…”

“…The basal levels of VASP phosphorylation at Ser 239 were comparable in freshly collected PLTs (from WB) and in APCs on Day 0, directly after apheresis, and increased significantly during storage, twofold on Day 2 and almost fivefold on Day 5 (Fig. ) . A quantity of 2 nmol/L DEA/NO induced a twofold higher VASP phosphorylation at Ser 239 in APCs on Day 0 compared to WB.…”

“…Profound data on the alterations of the inhibitory signaling pathways in PLTs under storage are lacking. Recently, we were able to demonstrate that phosphodiesterase 5A (PDE5A) activity decreases during storage of APCs, accompanied by increasing cGMP levels and enhanced basal VASP phosphorylation …”

Biochemistry of storage lesions of red cell and platelet concentrates: A continuous fight implying oxidative/nitrosative/phosphorylative stress and signaling

“…A key mechanism of action is the stimulation of intracellular guanylyl cyclase with resulting elevation of cGMP which affects various platelet cGMP effector systems including cGMP-dependent protein kinases [93]. Storage of apheresis-derived PLT concentrates (PCs) causes an impairment of the intracellular cGMP regulation with resulting reduced activating potential of PLTs [94,95]. Nevertheless, cGMP-independent mechanisms as well may contribute to the NO-mediated antiplatelet activity, for example by either chemically modifying biomolecules through nitrosylation and nitrosothiol formation or targeted protein tyrosine nitration via peroxynitrite formation [96].…”