Increased fibrinolytic mediators in IPF as potential contributors to pulmonary fibrosis and vascular remodeling

<b>Background:</b> IPF is associated to an important pulmonary vascular and tissular remodeling. Their mechanisms might involve the coagulation cascade through its role on matrix degradation. Microparticules (MP) are key fibrinolytic mediators so far unexplored in IPF. <b>Objectives:</b> To determine plasmatic levels of plasminogen activators (uPA and tPA) and inihibitor (PAI-1) in parallel of presence, levels and fibrinolytic activity of circulating MP. <b>Methods:</b> uPA, tPA and PAI-1 mRNAs in peripheral blood cells were quantitated using RT-PCR and plasmatic soluble levels by ELISA. MP cellular sub-populations were assessed using flow cytometry and their fibrinolytic activity through plasminogen activation kinetics (spectrophotometry) and zymography. <b>Results:</b> No difference was observed between IPF (n=54) and age-matched healthy controls (n=13) mRNAs of whole blood cells. In contrast, soluble uPA, tPA and PAI-1 in plasma were increased in IPF (p=0.0042, p=0.03 and 0.0017, respectively vs controls) as well as both endothelial and platelet-derived MP (respectively with p=0.0003 and 0.0014 vs controls). In addition, MP were active in generating plasmin (zymography) and this activity was increased vs controls (p=0.0042). <b>Conclusion:</b> Marked increases in circulating fibrinolytic mediators are present in IPF. Their potential contribution to fibrogenesis and vascular remodeling still needs to be determined. These data might add to the present hints to fibrogenesis and aberrant neoangiogenesis present in IPF.