Elena Rodríguez-Sánchez1, José Alberto Navarro-García1, Jennifer Aceves-Ripoll1, Gloria Álvarez-Llamas2, Julián Segura3, María G Barderas4, Luis Miguel Ruilope5, Gema Ruiz-Hurtado6. 1. Laboratorio Traslacional Cardiorrenal, Instituto de Investigación i+12, Hospital Universitario 12 de Octubre, Madrid, España. 2. Departamento de Inmunología, IIS-Fundación Jiménez Díaz, Madrid, España. 3. Laboratorio Traslacional Cardiorrenal, Instituto de Investigación i+12, Hospital Universitario 12 de Octubre, Madrid, España; Unidad de Hipertensión, Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, España. 4. Departamento de Fisiopatología Vascular, Hospital Nacional de Parapléjicos (HNP), SESCAM, Toledo, España. 5. Laboratorio Traslacional Cardiorrenal, Instituto de Investigación i+12, Hospital Universitario 12 de Octubre, Madrid, España; Unidad de Hipertensión, Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, España; Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, España; Escuela de Estudios de Doctorado e Investigación, Universidad Europea de Madrid, Madrid, España. 6. Laboratorio Traslacional Cardiorrenal, Instituto de Investigación i+12, Hospital Universitario 12 de Octubre, Madrid, España; Unidad de Hipertensión, Servicio de Nefrología, Hospital Universitario 12 de Octubre, Madrid, España. Electronic address: gemaruiz@h12o.es.
Abstract
BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMPs) are involved in deleterious tissue remodeling associated with target organ damage in renal disease. The aim of this study was to study the association between renal dysfunction and activity of the inflammatory metalloproteinase MMP-9 in hypertensive patients with mild-moderate chronic kidney disease (CKD). MATERIAL AND METHODS: Plasmatic active MMP-9, total MMP-9, tissue inhibitor of MMP-9 (TIMP-1), MMP-9/TIMP-1 ratio and MMP-9-TIMP-1 interaction were analyzed in 37 hypertensive patients distributed by estimated glomerular filtration rate (eGFR) in 3 groups:>90, 90-60 y 60-30mL/min/1.73 m2. RESULTS: Total MMP-9 was not different as eGFR declines. TIMP-1 was significantly increased in hypertensive patients with eGFR 60-30mL/min/1.73 m2 (P<.01 versus>90mL/min/1.73 m2). This relates to the significant decrease in the interaction between MMP-9-TIMP-1 observed in patients with eGFR 60-30mL/min/1.73 m2 (P<.01 versus>90mL/min/1.73 m2). Despite the systemic elevation of TIMP-1, active MMP-9 was significantly increased in hypertensive patients with eGFR 60-30mL/min/1.73 m2 (P<.05 and P<0.01 versus>90 and 90-60mL/min/1.73 m2, respectively). TIMP-1, active MMP-9 and MMP-9-TIMP-1 interaction significantly correlate with the decline in renal function, which was not observed with total MMP-9. CONCLUSIONS: The progression of CKD, even in stages where the decline of renal function is still moderate, is associated with an increase in MMP-9 activity, which could be considered as a potential therapeutic target.
BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMPs) are involved in deleterious tissue remodeling associated with target organ damage in renal disease. The aim of this study was to study the association between renal dysfunction and activity of the inflammatory metalloproteinase MMP-9 in hypertensivepatients with mild-moderate chronic kidney disease (CKD). MATERIAL AND METHODS: Plasmatic active MMP-9, total MMP-9, tissue inhibitor of MMP-9 (TIMP-1), MMP-9/TIMP-1 ratio and MMP-9-TIMP-1 interaction were analyzed in 37 hypertensivepatients distributed by estimated glomerular filtration rate (eGFR) in 3 groups:>90, 90-60 y 60-30mL/min/1.73 m2. RESULTS: Total MMP-9 was not different as eGFR declines. TIMP-1 was significantly increased in hypertensivepatients with eGFR 60-30mL/min/1.73 m2 (P<.01 versus>90mL/min/1.73 m2). This relates to the significant decrease in the interaction between MMP-9-TIMP-1 observed in patients with eGFR 60-30mL/min/1.73 m2 (P<.01 versus>90mL/min/1.73 m2). Despite the systemic elevation of TIMP-1, active MMP-9 was significantly increased in hypertensivepatients with eGFR 60-30mL/min/1.73 m2 (P<.05 and P<0.01 versus>90 and 90-60mL/min/1.73 m2, respectively). TIMP-1, active MMP-9 and MMP-9-TIMP-1 interaction significantly correlate with the decline in renal function, which was not observed with total MMP-9. CONCLUSIONS: The progression of CKD, even in stages where the decline of renal function is still moderate, is associated with an increase in MMP-9 activity, which could be considered as a potential therapeutic target.
Authors: Elena Rodríguez-Sánchez; José Alberto Navarro-García; Jennifer Aceves-Ripoll; Judith Abarca-Zabalía; Andrea Susmozas-Sánchez; Teresa Bada-Bosch; Eduardo Hernández; Evangelina Mérida-Herrero; Amado Andrés; Manuel Praga; Mario Fernández-Ruiz; José María Aguado; Julián Segura; Luis Miguel Ruilope; Gema Ruiz-Hurtado Journal: Biomolecules Date: 2020-03-26