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Circulating TIMP-1 is associated with hematoma volume in patients with spontaneous intracranial hemorrhage

Autores: Navarro Oviedo, Manuel; Munoz-Arrondo, R.; Zandio, B.; Marta-Enguita, J.; Bonaterra-Pastra, A. ; Rodríguez García, José Antonio; Roncal Mancho, Carmen; Páramo Fernández, José Antonio; Toledo Atucha, Estefanía; Montaner, J. ; Hernandez-Guillamon, M.; Orbe Lopategui, Josune (Autor de correspondencia)
Título de la revista: SCIENTIFIC REPORTS
ISSN: 2045-2322
Volumen: 10
Número: 1
Páginas: 10329
Fecha de publicación: 2020
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 (0.05-0.2mg/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 1ng/ml in TIMP-1 was associated with an increase of 0.14ml in haemorrhage (combined beta =0.14, 95% CI=0.08-0.21). Likewise, mice receiving TIMP-1 (0.2mg/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.