Association Between Expression of Mmp-2 and Mmp-9 Genes and Pathogenesis of Intracranial Hemorrhage in Severe Coagulation Factor Xiii Deficiency Publisher



Naderi M¹ ; Younesi MR² ; Dorgalaleh A³ ; Alizadeh S² ; Kazemi A³ ; Tabibian S² Show Affiliations
Source: Hematology (United Kingdom) Published:2015

Abstract

Background: Matrix metalloproteinases (MMPs) play a key role in the degradation of basement membrane and extracellular matrix in tissue remodeling, and are involved in pathogenesis of intracranial hemorrhage (ICH). Despite replacement therapy, ICH is by far the main cause of bleeding-related death among patients with severe factor XIII deficiency (FXIIID). The aim of this study is to evaluate the association between MMP-2 and MMP-9 genes expression and ICH in these patients. Materials and methods: Quantitative real-time reverse transcription (RT)-PCR assay was used to quantify MMP-2 and MMP-9 mRNAs in 42 specimens of patients with FXIIID including 18 case and 24 control groups. The comparative method of relative quantification (2–Delta-Delta-cCt) was utilized to analyze the expression level of each target gene. The expression level of glyceraldehyde-3-phosphate dehydrogenase was used to standardize the expression levels of MMPs. Results: Umbilical bleeding was the most common clinical manifestation among all patients. We found expression upregulation of MMP-9 gene in 13 patients (72.2%) in case and 3 patients (12.5%) in control group, indicating a significant difference between cases and controls for MMP-9 gene expression level (P = 0.001%)(CI 2.8–95.3). Conclusions: Our patients present with a wide spectrum of clinical symptoms, which are important in screening and diagnosis of patients with FXIIID. We hypothesized that the overexpression of MMP-9 due to polymorphisms or inflammation was associated with pathogenesis of ICH in FXIIID. This effect can be attenuated by nonspecific MMP inhibition to reduce hospitalization and death rates in these patients. © W. S. Maney & Son Ltd 2015.