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

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.

• Authors: Manuel Navarro-Oviedo, Roberto Muñoz-Arrondo, Beatriz Zandio, Juan Marta-Enguita, Anna Bonaterra-Pastra, Jose Antonio Rodríguez, Carmen Roncal, Jose A Páramo, Estefania Toledo, Joan Montaner, Mar Hernández-Guillamon, Josune Orbe
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 10329 (06 25 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32587306 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• TIMP1 protein, human
• Tissue Inhibitor of Metalloproteinase-1
• MMP7 protein, human
• Matrix Metalloproteinase 7

Topics

• Aged
• Aged, 80 and over
• Animals
• Biomarkers (blood)
• Disease Models, Animal
• Female
• Head (diagnostic imaging)
• Hematoma (blood, diagnosis, drug therapy, etiology)
• Humans
• Intracranial Hemorrhages (blood, complications, diagnosis, drug therapy)
• Male
• Matrix Metalloproteinase 7 (blood)
• Mice
• Prospective Studies
• Severity of Illness Index
• Tissue Inhibitor of Metalloproteinase-1 (blood, therapeutic use)
• Tomography, X-Ray Computed