Circulating TIMP-1 is associated with hematoma volume in patients with spontaneous intracranial hemorrhage
Navarro-Oviedo, Manuel (Universidad de Navarra)
Muñoz-Arrondo, Roberto (Instituto de Investigación Sanitaria de Navarra)
Zandio, Beatriz (Instituto de Investigación Sanitaria de Navarra)
Marta-Enguita, Juan (Instituto de Investigación Sanitaria de Navarra)
Bonaterra-Pastra, Anna (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Rodríguez, Jose Antonio (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Roncal, Carmen (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Páramo, Jose A. (Clínica Universidad de Navarra)
Toledo, Estefania (Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición)
Montaner, Joan (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Hernandez Guillamon, Maria Mar (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Orbe, Josune (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
Universitat Autònoma de Barcelona

Date:	2020
Abstract:	Matrix metalloproteinases (MMPs) are proteolytic zinc-endopeptidases regulated by tissue Inhibitors of matrix metalloproteinases (TIMPs). We evaluated the potential of MMPs and TIMPs as clinical tools for Intracranial Haemorrhage (ICH). Spontaneous non-traumatic ICH patients were recruited from two hospitals: Complejo Hospitalario de Navarra (CHN = 29) and Vall d'Hebron (VdH = 76). Plasmatic levels of MMP-1, −2, −7, −9, −10 and TIMP-1 and their relationship with clinical, radiological and functional variables were evaluated. We further studied the effect of TIMP-1 (0. 05-0. 2 mg/Kg) in an experimental tail-bleeding model. In CHN, TIMP-1 was associated with admission-hematoma volume and MMP-7 was elevated in patients with deep when compared to lobar hematoma. In VdH, admission-hematoma volume was associated with TIMP-1 and MMP-7. When data from both hospitals were combined, we observed that an increase in 1 ng/ml in TIMP-1 was associated with an increase of 0. 14 ml in haemorrhage (combined β = 0. 14, 95% CI = 0. 08-0. 21). Likewise, mice receiving TIMP-1 (0. 2 mg/Kg) showed a shorter bleeding time (p < 0. 01). Therefore, the association of TIMP-1 with hematoma volume in two independent ICH cohorts suggests its potential as ICH biomarker. Moreover, increased TIMP-1 might not be sufficient to counterbalance MMPs upregulation indicating that TIMP-1 administration might be a beneficial strategy for ICH.
Grants:	Ministerio de Economía y Competitividad PI15/01807 Instituto de Salud Carlos III PI19/00065
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Molecular biology ; Neuroscience ; Biomarkers ; Neurology
Published in:	Scientific reports, Vol. 10 (june 2020) , ISSN 2045-2322

DOI: 10.1038/s41598-020-67250-9
PMID: 32587306

10 p, 1.1 MB

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