Defibrotide reduces monocyte PAI-2 and procoagulant activity.
Defibrotide is a polydeoxyribonucleotide-derived anti-ischemic drug with multiple sites of action involving both plasmatic and cellular targets. This agent has been demonstrated to produce profibrinolytic, cytoprotective, and vaso-facilatory actions. Since monocytes are increased in the mediation of some of the pathophysiologic responses seen in ischemic disorders, the functional properties of these cells were investigated in experimental conditions to evaluate their behavior during resting and stimulated states. Defibrotide was supplemented in these systems to determine its modulatory action. In this investigation Defibrotide was found to decrease the PAI-1 levels and may indicate that this may be the mechanism for its profibrinolytic actions. Defibrotide was also found to reduce the procoagulant activity of monocytes in these experimental settings. Both PAI and procoagulant factors play an important role in the pathophysiology of inflammation, DIC, and ischemia. Defibrotide induced reduction of these two factors represents the mechanism whereby this agent produces its therapeutic action.
Abbate
R
R
Clinica Medica l e Cardiologia, University of Florence, Italy.
Gori
A M
AM
Martini
F
F
Attanasio
M
M
Comeglio
P
P
Giusti
B
B
Zarone
N
N
Francalanci
I
I
Prisco
D
D
Gensini
G F
GF
D001779:Blood Coagulation Factors / Q000187:drug effects*; D016207:Cytokines / Q000097:blood; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007511:Ischemia / Q000188:drug therapy*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000097:blood*; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
D001779:Blood Coagulation Factors; D016207:Cytokines; D005343:Fibrinolytic Agents; D017396:Plasminogen Activator Inhibitor 2; D011089:Polydeoxyribonucleotides; C036901:defibrotide; D013929:Thromboxane B2