β-Adrenergic Receptor Stimulation Transactivates Protease-Activated Receptor 1 via Matrix Metalloproteinase 13 in Cardiac Cells

Abstract

In this study, we demonstrate that β-AR stimulation leads to MMP-13 transactivation of PAR1 in both cardiac fibroblasts and cardiomyocytes and that this likely contributes to pathological activation of Gαq and ErbB receptor-dependent pathways in the heart. We propose that this mechanism may underlie the development of β-AR overstimulation-dependent cardiac dysfunction.