Tryptase Promotes the Profibrotic Phenotype Transfer of Atrial Fibroblasts by PAR2 and PPARγ Pathway

As shown in clinical and experimental studies, atrial fibrosis is an important mechanism for the occurrence and development of atrial fibrillation, the most common arrhythmia in the clinic with high disability and mortality. Some studies have shown the possible involvement of tryptase, a protease released by mast cells, in the fibrosis of heart tissues, but the effect and mechanism of tryptase on extracellular matrix (ECM) remodeling and atrial fibrosis is not clear yet.

This study evaluated the effects of tryptase on the proliferation, migration, ECM remodeling and the balance between matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) of fibroblasts by in vitro culture of atrial fibroblasts. The involvement of Protease activated receptor 2 (PAR2), platelet-derived growth factor receptor (PDGFR) or peroxisome proliferator-activated receptor (PPAR)γ were investigated with their respective antagonists.

Tryptase significantly increased the cell proliferation, the protein levels of Collagen I, fibronectin and laminin, migration ability and MMP (-1, -2) levels of atrial fibroblasts in a time-dependent manner. The TIMP (-1, -2) levels of atrial fibroblasts were significantly decreased. PAR2 antagonist FSLLRY-NH2 or PPARγ antagonist GW9662 significantly abolished these profibrotic effects of tryptase.

Tryptase may promote the profibrotic phenotype transfer of atrial fibroblasts by activating PAR2 and PPARγ. This finding may provide new strategies for the prevention of atrial fibrosis.