49. Impact of atrial fibrillation on platelet-predominate gene expression

Abstract

Platelets retain cytoplasmic mRNA and are capable of protein biosynthesis upon stimulation. We hypothesized that changes in flow hemodynamics, and extracel- lular matrix stimulation induced by non-valvular atrial fibrillation (NVAF) may impact platelet RNA content and therefore platelet activity in patients with this dysrhythmia. Expression of platelet predominate genes was assessed in consecutive NVAF patients before and 3–4 months after catheter ablation of pulmonary veins (CAPV). Results were compared to age and gender matched normal sinus rhythm (NSR) controls. RNA from isolated platelets were reverse-transcribed (Invitrogen), assayed against 22 genes (TaqMan) using real-time qPCR, and expressed as mean cycle threshold (ΔCt) (ABI Prism 7700 Sequence Detection System) using beta-2-microglobulin as endogenous control. All evaluated genes, except cathepsin A gene (CTSA), showed lower expression (higher ΔCt) in 103 NVAF patients compared to 55 NSR controls. At least 2-fold lower expression was found in 12 genes. Within this group, expression of insulin-like growth factor binding protein acid labile subunit gene (IGFALS) was more than 16th fold lower (more than four cycles; 17.0 ± 2.8 vs 12.5 ± 3.8, p < .001) and non-muscle cofilin gene (CFL1), prostacyclin receptor gene (PTGIR), and von Willebrand gene (VWF) were 4-fold lower compared to NSR controls. After CAPV, 7 genes demonstrated increased expression including IGFALS gene that showed 256-fold increase (8.3 ± 5.6 vs 16.6 ± 3.0, p < .001). Four genes had lower expression after CAPV but only one, tubulin gene (TUBA4A) had it lower by one cycle (2-fold). DD96 membrane associated protein gene (PDZK1IP) showed significantly higher expression in patients without recurrence of atrial fibrillation compared to those with confirmed or suspected recurrence.The altered flow hemodynamics associated with NVAF impacts platelet RNA content. Of these, measurable differences of IGFALS expression is notable. Changes of platelet gene expression following sinus rhythm restoration underscores the direct interaction between these two entities.