The organomercurial 4-aminophenylmercuric acetate, independent of matrix metalloproteinases, induces dose-dependent activation/ inhibition of platelet aggregation

Mathias T. Rosenfeldt; Michael Valentino; Salvatore Labruzzo; Lesley Scudder; Maria Pavlaki; Jian Cao; Jeffrey Vacirca; Wadie F. Bahou; Stanley Zucker

doi:10.1160/TH04-08-0541

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2005; 93(02): 326-330
DOI: 10.1160/TH04-08-0541

Platelets and Blood Cells

Schattauer GmbH

The organomercurial 4-aminophenylmercuric acetate, independent of matrix metalloproteinases, induces dose-dependent activation/ inhibition of platelet aggregation

Autor*innen

Mathias T. Rosenfeldt^*

¹Department of Medicine, Veterans Affairs Medical Center, Northport, New York, USA
Michael Valentino

¹Department of Medicine, Veterans Affairs Medical Center, Northport, New York, USA
Salvatore Labruzzo

¹Department of Medicine, Veterans Affairs Medical Center, Northport, New York, USA
Lesley Scudder

²Department of Medicine, State University of New York at Stony Brook, New York, USA
Maria Pavlaki

²Department of Medicine, State University of New York at Stony Brook, New York, USA
Jian Cao

²Department of Medicine, State University of New York at Stony Brook, New York, USA
Jeffrey Vacirca

¹Department of Medicine, Veterans Affairs Medical Center, Northport, New York, USA

²Department of Medicine, State University of New York at Stony Brook, New York, USA
Wadie F. Bahou^†

²Department of Medicine, State University of New York at Stony Brook, New York, USA
Stanley Zucker^†

¹Department of Medicine, Veterans Affairs Medical Center, Northport, New York, USA

²Department of Medicine, State University of New York at Stony Brook, New York, USA

Abstract

Summary

Matrix metalloproteinases (MMPs) play an important role in many biological and pathological processes including tissue remodeling, wound healing, inflammation, atherosclerosis, and cancer. Numerous publications have supported the concept that activated MMP-2 enhances agonist-induced platelet aggregation and activated MMP-9 inhibits platelet aggregation. In this study, we demonstrated that the organomercurial compound, 4-aminophenyl mercuric acetate (APMA), which is routinely employed to activate latent MMPs at a concentration of 1000 μ M, induces platelet aggregation at low concentration (5 μ M) and inhibits agonist-induced platelet aggregation at concentrations ≥ 50 μ M. Activated MMP-2, MMP-1, and MMP-9, following removal of APMA by ultrafiltration through an anisotropic membrane, exert no independent effect on platelet aggregation. Acetylsalicylic acid and BAPTA inhibited APMA-induced platelet aggregation indicating that the APMA mediated pathway of platelet activation is dependent upon thromboxane and calcium signaling. Zinc chelation with 1,10-phenanthroline, which inhibits zincdependent proteins including metalloproteinases, also abrogated platelet functional responses to APMA. Additional studies will be required to clarify the mechanism of the biphasic effect of APMA on platelet aggregation.

Keywords

Matrix metalloproteinases (MMP) - platelet aggregation - 4-aminophenylmercuric acetate (APMA)

Volltext

Referenzen

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