TITLE:
Alterations in fibrinolytic system proteins PAI-1, MMP-3, MMP-8, TIMP-1 and TIMP-2 in post-cholecystectomy bile duct injury
AUTHORS:
José Manuel Hermosillo-Sandoval, Luis Miguel Román-Pintos, Adolfo Daniel Rodríguez-Carrizález, Ernesto Germán Cardona-Muñoz, Fermín Paul Pacheco-Moisés, Genaro Gabriel Ortiz, Alejandra Guillermina Miranda-Díaz
KEYWORDS:
Cholecystectomy; Bile Duct Injury (BDI); Plasminogen Activator Inhibitor Type 1 (PAI-1); Tissue Inhibitors of Metalloproteinases (TIMP’s); Metalloproteinases (MMP’s)
JOURNAL NAME:
Journal of Biomedical Science and Engineering,
Vol.6 No.8B,
August
16,
2013
ABSTRACT: Introduction: In bile duct injuries (BDI), cholestasis and cholangitis can alter the fibrinolytic system by promoting an increase of extracellular matrix depositions which favor an imbalance between metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Materials and Methods: Levels of PAI-1, MMP-3, MMP-8, TIMP-1 and TIMP-2 in 35 patients with post-cholecystectomy BDI by complete biliary obstruction were measured and compared to a healthy control group. Sirius red staining and immune staining for MMP-3 and MMP-8 were also undertaken in liver biopsies. Results: Levels of PAI-1, TIMP-1, TIMP-2 and MMP-8 were higher in BDI than healthy controls: 15 ± 2 ng/mL vs 7.1 ± 2 ng/mL (p 0.024); 539 ± 64 ng/mL vs 256 ± 13 ng/mL (p p p 2 vs. 22865.7 ± 3865 μm2 in healthy controls (p 2 vs. 30744.2 ± 5810.2 μm2 (p 2 vs. 116337.9 ± 24803.3 μm2 (p 0.55). These results suggest an imbalance between fibrogenic/fibrinolytic protein levels. Interestingly, expression of the fibrinolytic protein MMP-8 was increased in serum and liver biopsies in BDI. Conclusion: We found an imbalance of profibrogenic molecules which promote extracellular matrix deposition. The over-expression of fibrinolytic proteins such as MMP-8 could limit liver fibrosis, preventing hepatic dysfunction in post-cholecystectomy BDI.