Glycosaminoglycan sulodexide inhibition of MMP-9 gelatinase secretion and activity: possible pharmacological role against collagen degradation in vascular chronic diseases.
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.
Department of Biomolecular Sciences, Section of Clinical Biochemistry, Unit of Cell Biology, University "Carlo Bo", Via O. Ubaldini 7, Urbino (PU), Italy. ferdinando.mannello@uniurb.it
Ferdinando
F
Mannello
Virginia
V
Medda
Daniela
D
Ligi
Joseph D
JD
Raffetto
D000328:Adult; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006025:Glycosaminoglycans / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D011446:Prospective Studies; D020298:U937 Cells; D014652:Vascular Diseases / Q000188:drug therapy / Q000503:physiopathology
D006025:Glycosaminoglycans; D061965:Matrix Metalloproteinase Inhibitors; C007858:glucuronyl glucosamine glycan sulfate; D003094:Collagen; D020780:Matrix Metalloproteinase 9