01 January 2001
Matrix Metalloproteinase-2 in Platelet Adhesion to Fibrinogen: Interactions With Nitric Oxide
Alfredo Martinez, Eduardo Salas, Anna Radomski, Marek W RadomskiMed Sci Monit 2001; 7(4): BR646-651 :: ID: 421090
Abstract
BACKGROUND: Matrix metalloproteinase-2 (MMP-2) has been shown to activatea non-thromboxane, non-ADP pathway of platelet aggregation. In contrast, nitric oxide (NO) is known toinhibit platelet adhesion and aggregation. Therefore, we have studied the release of MMP-2 during plateletadhesion to fibrinogen, the effects of phenanthrolione, an MMP-2 inhibitor, on adhesion and the interactionsof inhibitor with a NO donor, S-nitroso-N-acetyl-D, L-penicillamine (SNAP).
MATERIAL AND METHODS: Humanplatelets were isolated from blood of healthy volunteers and platelet adhesion to fibrinogen-coated plateswas studied by measuring thrombin-stimulated release of platelet a-granule constituent, platelet factor4. In addition, the mode of action of phenanthroline and NO on platelets was investigated by assayingthe levels of intraplatelet cyclic GMP.
RESULTS: Thrombin-stimulated platelet adhesion to fibrinogen wasassociated with increased release of MMP-2 from platelets. Phenanthroline (0.1-100 KM) reduced plateletadhesion to fibrinogen. The adhesion was also inhibited by SNAP (0.1-100 KM), an effect abolished by1H-[1,2,4] oxadiazolol [4,3,-a] quinoxalin-1-one (ODQ), a selective inhibitor of the soluble guanylatecyclase. Co-administration of phenanthroline and SNAP resulted in a synergistic inhibition of plateletadhesion, an effect that was not associated with enhanced cyclic GMP generation by platelets. Furthermore,ODQ did not reverse the synergistic effect of these compounds on adhesion.
CONCLUSIONS: 1. MMP-2 promotesplatelet adhesion to fibrinogen. 2. Phenanthroline and NO synergize to inhibit platelet adhesion to fibrinogenacting through a cyclic GMP-independent mechanism(s).
Keywords: Matrix metalloproteinase-2, Nitric Oxide, platelet adhesion
Editorial
01 March 2024 : Editorial
Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and Transfusion-Dependent β-ThalassemiaDOI: 10.12659/MSM.944204
Med Sci Monit 2024; 30:e944204
In Press
21 Feb 2024 : Clinical Research
Potential Value of HSP90α in Prognosis of Triple-Negative Breast CancerMed Sci Monit In Press; DOI: 10.12659/MSM.943049
22 Feb 2024 : Review article
Differentiation of Native Vertebral Osteomyelitis: A Comprehensive Review of Imaging Techniques and Future ...Med Sci Monit In Press; DOI: 10.12659/MSM.943168
23 Feb 2024 : Clinical Research
A Study of 60 Patients with Low Back Pain to Compare Outcomes Following Magnetotherapy, Ultrasound, Laser, ...Med Sci Monit In Press; DOI: 10.12659/MSM.943732
26 Feb 2024 : Clinical Research
Predictive Value of Combined HbA1c and Neutrophil-to-Lymphocyte Ratio for Diabetic Peripheral Neuropathy in...Med Sci Monit In Press; DOI: 10.12659/MSM.942509
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952