<i>NET</i> silencing by <i>let-7i</i> in postural tachycardia syndrome.

Abstract

While strongly implicated in postural tachycardia syndrome (POTS), considerable controversy exists regarding norepinephrine transporter (<i>NET</i>) loss of function. POTS is characterized by the clinical symptoms of orthostatic intolerance, lightheadedness, tachycardia, and syncope or near syncope with upright posture. Abnormal sympathetic nervous system activity is typical, of a type which suggests dysfunction of the NET, with evidence that the gene responsible is under tight epigenetic control. Using RNA of isolated chromatin combined with massive parallel sequencing (RICh-seq) we show that <i>let-7i</i> miRNA suppresses <i>NET</i> by methyl-CpG-binding protein 2 (MeCP2). Vorinostat restores epigenetic control and <i>NET</i> expression in leukocytes derived from POTS participants.