NET silencing by let-7i in postural tachycardia syndrome

Abdul Waheed Khan, Mark Ziemann, Susan J. Corcoran, Harikrishnan K N, Jun Okabe, Haloom Rafehi, Scott S. Maxwell, Murray D. Esler, Assam El-Osta

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16 Citations (Scopus)

Abstract

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 control and NET expression in leukocytes derived from POTS participants.

Original languageEnglish
Article numbere90183
Number of pages11
JournalJCI Insight
Volume2
Issue number6
DOIs
Publication statusPublished - 23 Mar 2017

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