Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia

Purinergic Signal. 2016 Sep;12(3):521-35. doi: 10.1007/s11302-016-9518-3. Epub 2016 May 23.

Abstract

Previous studies showed that the upregulation of the P2X7 receptor in cervical sympathetic ganglia was involved in myocardial ischemic (MI) injury. The dysregulated expression of long noncoding RNAs (lncRNAs) participates in the onset and progression of many pathological conditions. The aim of this study was to investigate the effects of a small interfering RNA (siRNA) against the NONRATT021972 lncRNA on the abnormal changes of cardiac function mediated by the up-regulation of the P2X7 receptor in the superior cervical ganglia (SCG) after myocardial ischemia. When the MI rats were treated with NONRATT021972 siRNA, their increased systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), low-frequency (LF) power, and LF/HF ratio were reduced to normal levels. However, the decreased high-frequency (HF) power was increased. GAP43 and tyrosine hydroxylase (TH) are markers of nerve sprouting and sympathetic nerve fibers, respectively. We found that the TH/GAP43 value was significantly increased in the MI group. However, it was reduced after the MI rats were treated with NONRATT021972 siRNA. The serum norepinephrine (NE) and epinephrine (EPI) concentrations were decreased in the MI rats that were treated with NONRATT021972 siRNA. Meanwhile, the increased P2X7 mRNA and protein levels and the increased p-ERK1/2 expression in the SCG were also reduced. NONRATT021972 siRNA treatment inhibited the P2X7 agonist BzATP-activated currents in HEK293 cells transfected with pEGFP-P2X7. Our findings suggest that NONRATT021972 siRNA could decrease the upregulation of the P2X7 receptor and improve the abnormal changes in cardiac function after myocardial ischemia.

Keywords: Long noncoding RNA; Myocardial ischemia; P2X7 receptor; Superior cervical ganglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • HEK293 Cells
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Myocardial Ischemia / metabolism*
  • Myocardial Ischemia / physiopathology
  • Patch-Clamp Techniques
  • RNA, Long Noncoding / metabolism*
  • RNA, Long Noncoding / pharmacology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptors, Purinergic P2X7 / biosynthesis*
  • Superior Cervical Ganglion / metabolism*
  • Sympathetic Nervous System / physiopathology
  • Up-Regulation

Substances

  • RNA, Long Noncoding
  • Receptors, Purinergic P2X7
  • long non-coding RNA NONRATT021972, rat