ABSTRACT
Atrial fibrillation (AF) is the most frequently diagnosed cardiac arrhythmia worldwide. Patients with permanent atrialfibrillation are at an increased risk of developing valvular heart disease. Atrial fibrosis occurs in this pathophysiologicalsetting. LIM kinase 1 (LIMK1) is a serine/threonine kinase that regulates microtubule stability and actin polymerization infibroblasts. LIMK1 has been implicated in the pathogenesis of atrial fibrillation. Clinical data and biopsies of the right atrialappendage were collected from 50 patients with valvular heart disease who underwent heart valve replacement surgery.Data from patients with permanent atrial fibrillation (AF) and patients with sinus rhythm (SR) were compared. We foundthat AF patients had upregulated expression of LIMK1 as well as higher fibrosis. Transforming growth factor-b (TGF-b)stimulation induced the differentiation of cardiac fibroblasts into myofibroblasts as well as upregulated expression ofLIMK1. Downregulation of LIMK1 by siRNA inhibited TGF-b induced fibroblast-myofibroblast transition, as evidencedby the downregulation of the expression of several differentiation markers, namely alpha-smooth muscle actin and type Iand III collagen. Our findings revealed that increased LIMK1 protein levels may contribute to atrial fibrosis, and suggestedthat LIMK1 might be involved in AF development by promoting fibrogenesis associated with TGF-b.