RESUMEN
OBJECTIVES: To describe and compare the evolution of digital pressure on both hands during a dialysis session in patients without digital ischemia, and to identify the parameters influencing the digital pressure. MATERIALS: Patients with an upper limb vascular access were prospectively included. Digital systolic pressure on the third finger of both hands measured by photoplethysmography and brachial systolic pressure were recorded before dialysis (H0) and every hour (from H1 to H4). RESULTS: Among 53 patients, 49 were included (exclusions: one surgery for ischemia, one hand tremor, two no consent). None of them had digital ischemia. Digital pressure homolateral to the vascular access was significantly lower compared with controlateral side before and during dialysis. Digital pressure significantly decreased on both sides during dialysis. Brachial pressure decreased significantly compared to H0. Only the brachial pressure decrease was correlated with the decrease of digital pressure. The digital pressure was less than 30 mmHg in six patients. No evidence of digital ischemia was reported after a 6-month follow-up. CONCLUSION: To our knowledge, this is the first study showing a significant decrease of digital pressure in both hands during hemodialysis in patients without digital ischemia. Further studies are necessary to investigate which parameters can affect digital pressure and to look for clinical consequence of this measurement.
Asunto(s)
Presión Sanguínea , Dedos/irrigación sanguínea , Fallo Renal Crónico/terapia , Diálisis Renal , Adulto , Anciano , Anciano de 80 o más Años , Determinación de la Presión Sanguínea/métodos , Arteria Braquial , Femenino , Humanos , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Fotopletismografía , Estudios ProspectivosRESUMEN
Matrix metalloproteinase 2 (MMP2) has been reported to be secreted by collagen-stimulated platelets, and active MMP2 has been shown to play a role in platelet aggregation. It has been demonstrated that MMP2 activation is dependent on the complex (membrane type 1 [MT1]-MMP/tissue inhibitor of MMP2 [TIMP2]) receptor and MMP2. We have investigated human platelets as a possible source of MT1-MMP, and we have studied its role in MMP2 activation and in platelet aggregation. Gelatin zymograms showed the existence of MMP2 at proforms (68 kd) and activated-enzyme forms (62-59 kd) in supernatants of resting and activated platelets, respectively. No gelatinolytic activity was associated with the platelet pellet after aggregation, suggesting a total release of MMP2 during cell activation. By Western blot analysis in nonreduced conditions, MT1-MMP was found on resting platelet membranes in 2 forms-the inactive 45-kd form and an apparent 89-kd form, which totally disappeared under reduced conditions. After platelet degranulation, only the 45-kd form was detected. Reverse transcription-polymerase chain reaction experiments showed the expression in platelets of messenger RNA encoding for MMP2, MT1-MMP, and TIMP2. Flow cytometry analysis showed that MT1-MMP, MMP2, and TIMP2 expressions were enhanced at the activated platelet surface. MMP inhibitors, recombinant TIMP2, and synthetic BB94 inhibited collagen-induced platelet aggregation in a concentration-dependent manner, indicating the role of activated MT1-MMP in the modulation of platelet function. In conclusion, our results demonstrate the expression of the trimolecular complex components (MT1-MMP/TIMP2/MMP2) by blood platelets as well as the ability of MMP inhibitors to modulate the aggregating response.
Asunto(s)
Plaquetas/fisiología , Metaloproteinasa 2 de la Matriz/sangre , Metaloendopeptidasas/sangre , Agregación Plaquetaria/fisiología , Inhibidor Tisular de Metaloproteinasa-2/sangre , Colágeno/farmacología , Activación Enzimática , Regulación de la Expresión Génica , Humanos , Técnicas In Vitro , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasas de la Matriz Asociadas a la Membrana , Metaloendopeptidasas/genética , Fenilalanina/análogos & derivados , Fenilalanina/farmacología , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Proteasas/farmacología , ARN Mensajero/genética , Tiofenos/farmacología , Inhibidor Tisular de Metaloproteinasa-2/efectos de los fármacos , Inhibidor Tisular de Metaloproteinasa-2/genéticaRESUMEN
BACKGROUND: Matrix metalloprotease 2 (MMP2) is secreted in a latent inactive form (pro-MMP2) that is activated on the cell surface by a membrane-type 1 MMP (MT1-MMP) in the presence of the tissue inhibitor of MMP (TIMP2). In spite of evidence for the synthesis of MT1-MMP shown by immunoblotting, immunocytochemistry and RT-PCR, and of TIMP2, MMP2 was found exclusively in a latent form in human mesangial cells (HMC) serum-free culture medium. METHODS AND RESULTS: On purified membranes of HMC, MT1-MMP was found in a 63 kD latent form and as a faint band of 55 kD. The 55 kD band was also present in the ultracentrifuged conditioned medium and likely represented MT1-MMP cleaved from its transmembrane domain, since Northern blot analysis showed only one transcription product. The addition of urokinase plasminogen activator (uPA, 100 nM) to HMC membranes induced the activation of pro-MMP2 via the activation of latent membrane-associated MT1-MMP as reflected by the cleavage of the 63 and 55 kD forms. In addition, when the conditioned medium was successively incubated with uPA and alpha 2-macroglobulin and analyzed by immunoblotting, MT1-MMP decreased, indicating that the soluble MT1-MMP was in a latent form and was activated by uPA. CONCLUSION: Our results provide the first evidence, to our knowledge, of the existence of a soluble latent form of MT1-MMP secreted by primary human cells in culture, confirming that MT1-MMP is an ectoenzyme, and show that uPA can regulate MT1-MMP activity in a soluble phase.