Fibrinolytic activity is associated with presence of cystic media degeneration in aneurysms of the ascending aorta

International audienceAims Thoracic Ascending Aortic Aneurysms (TAA) are characterized by elastic fibre breakdown and cystic medial degeneration within the aortic media, associated with progressive SMC rarefaction. The TGF-β/Smad2 signaling pathway is involved in this process. Since pericellular fibrinolytic system activation is able to degrade adhesive proteins, activate MMPs, induce SMC disappearance and increase the bio-availability of TGF-β, we explored the plasminergic system in TAA. Methods and Results Ascending aortas (21 controls and 19 TAAs (of 3 different aetiologies)) were analyzed. Immunohistochemistry showed accumulation of t-PA, u-PA & plasmin in TAAs, associated with remaining SMCs. Over-expression of t-PA, and u-PA was confirmed by RT-PCR, immunoblotting and zymography on TAA extracts and culture medium conditioned by TAA. Plasminogen was present on the SMC surface and inside cytoplasmic vesicles, but plasminogen mRNA was undetectable in TAA medial layer. Plasmin-antiplasmin complexes were detected in TAA-conditioned medium and activation of the fibrinolytic system was associated with an increased fibronectin turnover. Fibronectin-related material was detected immunohistochamically in dense clumps around SMCs and co-localized with Latent TGF-β Binding Protein-1. Conclusions These observations indicate that the fibrinolytic pathway could play a critical role in TAA progression, via direct or indirect impact on ECM and consecutive modulation of TGF-β bio-availability