NET silencing by let-7i in postural tachycardia syndrome
Abdul Waheed Khan, Mark Ziemann, Susan J Corcoran, KN Harikrishnan, Jun Okabe, Haloom Rafehi, Scott S Maxwell, Murray D Esler, Assam El-Osta
JCI INSIGHT | AMER SOC CLINICAL INVESTIGATION INC | Published : 2017
While strongly implicated in postural tachycardia syndrome (POTS), considerable controversy exists regarding norepinephrine transporter (NET) 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 let-7i miRNA suppresses NET by methyl-CpG-binding protein 2 (MeCP2). Vorinostat restores epigenetic contro..View full abstract
Awarded by National Health and Medical Research Council (NHMRC)
Awarded by NHMRC-NFSC
We would like to acknowledge Gautam Vaddadi and Elisabeth Lambert (Baker IDI Heart and Diabetes Institute) who performed the head-up tilt (HUT) studies. This study was supported by a National Health and Medical Research Council (NHMRC) program grant ME, research fellowship AE (1070386 and APP0526681), and NHMRC-NFSC joint program AE (APP1113188). This work was supported in part by the Victorian Government's Operational Infrastructure Support Program.