Publicaciones científicas

Circulating TIMP-1 Is Associated With Hematoma Volume in Patients With Spontaneous Intracranial Hemorrhage

25-jun-2020 | Revista: Scientific Reports

Manuel Navarro-Oviedo 1, Roberto Muñoz-Arrondo 2, Beatriz Zandio 2, Juan Marta-Enguita 1  2, Anna Bonaterra-Pastra 3, Jose Antonio Rodríguez 1  4  Carmen Roncal 1  4, Jose A Páramo 1  4  5, Estefania Toledo 6  7, Joan Montaner 3, Mar Hernández-Guillamon 3, Josune Orbe 8  9

(1) Laboratory of Atherothrombosis, CIMA, Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra, IdisNA, Pamplona, Spain.
(2) Neurology Service, Complejo Hospitalario de Navarra, IdisNA, Pamplona, Spain.
(3) Neurovascular Research Laboratory, Vall d´Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
(4) Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.
(5) Haematology Service, Clínica Universidad de Navarra, Pamplona, Spain.
(6) Department of Preventive Medicine and Public Health, School of Medicine, Universidad de Navarra, IdiSNA, Pamplona, Spain.
(7) Centro de Investigación Biomédica en Red en Fisiopatología de la Obesidad y Nutrición (CIBEROBN), ISCIII, Madrid, Spain.
(8) Laboratory of Atherothrombosis, CIMA, Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra, IdisNA, Pamplona, Spain. josuneor@unav.es.
(9) Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.


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.

CITA DEL ARTÍCULO  Sci Rep . 2020 Jun 25;10(1):10329.  doi: 10.1038/s41598-020-67250-9

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