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.
Keywords: Chronic venous disease, dermatan sulphate, glycosaminoglycan, matrix metalloproteinases, plasma, sulodexide, U937 cell line.
Current Vascular Pharmacology
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.
Export Options
About this article
Cite this article as:
Mannello Ferdinando, Medda Virginia, Ligi Daniela and Raffetto Joseph D., Glycosaminoglycan Sulodexide Inhibition of MMP-9 Gelatinase Secretion and Activity: Possible Pharmacological Role Against Collagen Degradation in Vascular Chronic Diseases, Current Vascular Pharmacology 2013; 11 (3) . https://dx.doi.org/10.2174/1570161111311030010
DOI https://dx.doi.org/10.2174/1570161111311030010 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
Call for Papers in Thematic Issues
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Nanocarriers for Effective Topical Delivery of Anti-Infectives
Current Nanoscience Plasmodium Drug Targets Outside the Genetic Control of the Parasite
Current Pharmaceutical Design Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: “Reverse Pharmacology” and “Bedside to Bench” Approach
Current Drug Targets Synthesis of Rutin Derivatives to Enhance Lipid Solubility and Development of Topical Formulation with a Validated Analytical Method
Current Drug Delivery Medical Treatment of Chronic Venous Insufficiency
Vascular Disease Prevention (Discontinued) Oral Inflammation and Bacteremia: Implications for Chronic and Acute Systemic Diseases Involving Major Organs
Cardiovascular & Hematological Disorders-Drug Targets The Role of Matrix Gla Protein (MGP) in Vascular Calcification
Current Medicinal Chemistry Inflammation and Thrombophilia in Pregnancy Complications: Implications for Risk Assessment and Clinical Management
Cardiovascular & Hematological Disorders-Drug Targets A Qualitative and Quantitative Study of the Innervation of the Human Non Pregnant Uterus
Current Protein & Peptide Science Essentials of Daflon 500 mg: From Early Valve Protection to Long-Term Benefits in the Management of Chronic Venous Disease
Current Pharmaceutical Design The Effects of Sevoflurane or Remifentanil on the Stress Response to Surgical Stimulus
Current Pharmaceutical Design The Clinical Spectrum of Nephrogenic Systemic Fibrosis
Current Rheumatology Reviews Effect of a Peptide Construct on Differentiated Macrophage MMP-2 and MMP-9 Levels of Varicose Patients
Current Pharmaceutical Design L-PRP/L-PRF in Esthetic Plastic Surgery, Regenerative Medicine of the Skin and Chronic Wounds
Current Pharmaceutical Biotechnology Review of Erectile Dysfunction in Diabetic Animal Models
Current Diabetes Reviews Microbial Agents, Immune Function and Atheromatosis: The Chlamydophila pneumoniae Role
Current Immunology Reviews (Discontinued) New Technologies: Non-Hormonal Female Contraception
Current Women`s Health Reviews Anti-inflammatory Effects of Mesenchymal Stem Cells and their Secretomes in Pneumonia
Current Pharmaceutical Biotechnology Milk Thistle: A Future Potential Anti-Osteoporotic and Fracture Healing Agent
Current Drug Targets Cellular Mechanisms of Bypass Vein Graft Arterialization and Approaches to Attenuate Graft Remodeling
Vascular Disease Prevention (Discontinued)