ROCK (RhoA/Rho Kinase) activation in atrial fibrillation: molecular pathways and clinical implication.

Among the complex mechanisms of AF pathogenesis, intracellular calcium overload and oxidative stress play a major role, both triggered by inflammatory processes. The additional basic event taking place in AF is atrial fibrotic remodeling, again triggered by oxidative stress, which is determined by connexins rearrangement and differentiation of fibroblasts into active collagen-secreting myofibroblasts. RhoA/ROCK system is the final pathway of a wide spectrum of molecular effectors such as Angiotensin II, platelet-derived growth factor, connective tissue growth factor and transforming growth factor β, that overall determine calcium dysregulation and pro-fibrotic remodeling. Both in experimental and clinical studies, RhoA/ROCK activation has been linked to superoxide ion production, fibrotic remodeling and connexins rearrangement, with important con-sequences for AF pathogenesis. ROCK pathway inhibition may therefore be a therapeutic or pre-ventive target for special AF subgroups of patie...