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