Unnatural milieu: Thrombus after transcatheter mitral valve replacement

• What the article teaches Transcatheter heart valve thrombosis in the mitral position causes increased valve gradients, valve dysfunction, and symptoms, and may be associated with lack of therapeutic anticoagulation.
• How it will impact practice Anticoagulation with a vitamin K antagonist should be considered in all patients undergoing transcatheter mitral valve replacement.
• What new research/study would help answer the question posed Efficacy, optimal duration, and safety of anticoagulation therapy, balancing reduced thrombosis against increased bleeding risk, needs to be assessed in larger cohort studies and prospective trials.

     

Gene and protein expression of proteinase-activated receptor-1, 2 in a murine model of acute graft host disease

Proteinase-activated receptors (PARs) are a novel subclass of seven transmembrane-spanning, G protein-coupled receptors. PAR-1 and PAR-2 are widely expressed in a variety of cells and are found to be involved in many physiological and pathological processes including inflammation and immune response. However, little is known about the function of PAR-1, 2 in acute graft vs host disease (GVHD). In the present study, we first detected the expression of PAR-1, 2 protein and mRNA in a murine model of acute GVHD using the methods of immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction (PCR). Syngeneic hematopoietic stem cell transplantation (HSCT) mice served as controls. The relative gene expression level of PAR-1 was significantly increased in the skin, liver, small intestine of allogeneic HSCT mice (in skin: 0.039±0.013 vs 0.008±0.002 of controls, P=0.009; in liver: 0.165±0.006 vs 0.017±0.006 of controls, P=0.004; in small intestine: 0.215±0.009 vs 0.016±0.002 of controls, P=0.003), but not in the stomach, lung and kidney of allogeneic HSCT mice (P>0.05). PAR-2 mRNA expression in the liver and small intestine of allogeneic HSCT mice (in liver: 0.010±0.002 vs 0.003±0.001 of controls, P=0.008; in small intestine: 0.006±0.001 vs 0.003±0.001 of controls, P=0.024) was increased significantly, but PAR-2 mRNA expression in the other organs (P>0.05) was not found to be significantly elevated. PAR-1, 2 protein expression was in accordance with the mRNA expression, as shown by Western blot. Using immunohistochemistry the present study demonstrated that there was strong PAR-1, 2 immunoreactivity in the epithelial cell and vascular endothelial cell of target organs of acute GVHD. Our findings of markedly increased expression of PAR-1, 2 in target organs of acute GVHD suggest that PAR-1 and PAR-2 may play an important role in the pathogenesis of acute GVHD.