Title:Glycosaminoglycan Sulodexide Inhibition of MMP-9 Gelatinase Secretion and Activity: Possible Pharmacological Role Against Collagen Degradation in Vascular Chronic Diseases
Volume: 11
Issue: 3
Author(s): Ferdinando Mannello, Virginia Medda, Daniela Ligi and Joseph D. Raffetto
Affiliation:
Keywords:
Chronic venous disease, dermatan sulphate, glycosaminoglycan, matrix metalloproteinases, plasma, sulodexide,
U937 cell line.
Abstract: We evaluated the effects of the glycosaminoglycan sulodexide (SDX; antithrombotic/profibrinolytic drug) on
the activity and release of matrix metalloproteinases (MMPs) in human blood. This was a prospective non-randomized
study, analyzing by zymography and ELISA the in vitro effects of SDX on pro-enzyme, complexed, and active MMP
forms in plasma and serum from 60 healthy donors, and in U-937 leukemia cell line. The levels and zymographic profile
of MMP-2 did not show significant changes among samples and during SDX treatments. However, pro- and complexed
forms of MMP-9 were strongly affected by SDX treatment (P<0.001), with significant decrease of MMP-9 secretion from
white blood cells in a dose-dependent fashion (P<0.0001), without any displacement of MMP prodomains. The mechanism
of reduced release of MMP-9 forms from leukocytes and inhibition of proteolytic activity due to SDX treatment may
support the hypothesis that drugs based upon inhibitors of MMP-9 activity may provide a therapeutic tool for the underlying
pathological destruction of extracellular matrix, and offering novel pharmacologic applications for chronic inflammatory
vascular diseases, including varicose vein and chronic venous diseases associated with enhanced MMP activation in
blood and limbs.
