Increased Expression of Secretory Leukocyte Protease Inhibitor (SLPI) In Mononuclear Cells From Patients with Deep Vein Thrombosis

Abstract 1232

Deep venous thrombosis (DVT) is a common and potentially fatal condition affecting 1% to 2% of the population worldwide, with an annual incidence of 1 in 500. Several studies have demonstrated the association between inflammation and DVT. In this study, we performed a comparative analysis of gene expression from mRNA extracted from leukocytes of 20 patients with previous DVT of the lower limbs (14F/6M; mean age: 39.7 years). An array of inflammation-related genes was selected for this study. Patients were divided in subgroups: (1) spontaneous DVT (n=10; 7F/3M). (2) risk factor-associated DVT (n=6; 4F/2M), in whom risk factor included oral contraceptive, pregnancy, protein C or S deficiencies, and FV Leiden heterozigosity. (3) Patients with antiphospholipid syndrome (APS)-associated DVT (n=4; 3F/1M). Nine healthy volunteers (7F/2M) were used as controls. Using bioarray technology, 60 upregulated (UR) and 56 downregulated (DR) genes were found in DVT patients when compared to healthy volunteers. UR genes were related to immune response, inflammation and proteolysis, and DR genes were related to transcription regulation, signal transduction and inflammation. Gene expression of the SLPI, Caspase-4 precursor (CASP4), Cartilage-associated protein precursor (CRATP) and eukaryotic translation elongation factor 1 alpha 2 (EEF1A2) presented the most significant differences in expression and were then analyzed by qPCR for validation of the results. Statistical analysis was performed by the Mann-Whitney test. No significant differences were confirmed in the expression of CASP4, CRTAP and EEF1A2 between patients and controls. However, a three-fold increased in the expression of SLPI was confirmed in DVT patients compared to controls (p=0.0381). Secretory leukocyte protease inhibitor (SLPI) is synthesized and secreted by mononuclear cells to the site of inflammation in response to cytokines and TNF. Increased SLPI expression could be a result of the inflammatory response that follows DVT. SLPI, a protease inhibitor, could function as a protective mechanism that could neutralize any excess protease load and protect host tissue. Further studies to investigate the role of SLPI in the pathogeneis of DVT and its complications are warranted.