ROCK (RhoA/Rho Kinase) Activation in Atrial Fibrillation: Molecular Pathways and Clinical Implications



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 collagensecreting
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 consequences
for AF pathogenesis. ROCK pathway inhibition may therefore be a therapeutic or preventive
target for special AF subgroups of patients.
