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.
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Change history
03 October 2020
Due to the authors��� carelessness, we used mistakenly images in Fig. 5B(B1) for P2X7 immunoreactivity in MI group(the second on the upper left) and MI+BBG group (The first one on the upper left).
Abbreviations
- ATP:
-
Adenosine triphosphate
- CK:
-
Creatine kinase
- CK-MB:
-
Creatine kinase isoform MB
- cTn-I:
-
Cardiac troponin I
- DBP:
-
Diastolic blood pressure
- ECG:
-
Electrocardiogram
- ELISA:
-
Enzyme-linked immunosorbent assay
- EPI:
-
Epinephrine
- HE staining:
-
Hematoxylin and eosin staining
- ERK1/2:
-
Extracellular signal-regulated protein kinases
- HF:
-
High frequency
- HR:
-
Heart rate
- HRV:
-
Heart rate variability
- IOD:
-
Integrated optical density
- IL-6:
-
Interleukin-6
- ISH:
-
In situ hybridization
- LCA:
-
Left coronary artery
- LDH:
-
Lactate dehydrogenase
- LF:
-
Low frequency
- MI:
-
Myocardial ischemia
- NE:
-
Norepinephrine
- PCR:
-
Polymerase chain reaction
- p-ERK1/2:
-
Phosphorylated extracellular signal-regulated protein kinases
- SBP:
-
Systolic blood pressure
- TH:
-
Tyrosine hydroxylase
- TNF-α:
-
Tumor necrosis factor-α
- SCG:
-
Superior cervical ganglia
- siRNA:
-
Small interfering RNA
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Acknowledgments
These studies were supported by grants (nos. 81570735, 31560276, 81560219, 81560529, 81460200, 81171184, 31060139, and 81200853) from the National Natural Science Foundation of China, a grant (no. 20151122040105) from the Technology Pedestal and Society Development Project of Jiangxi Province, a grant (no. 20142BAB205028) from the Natural Science Foundation of Jiangxi Province, and grants (nos. GJJ13155 and GJJ14319) from the Educational Department of Jiangxi Province.
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Guihua Tu, Lifang Zou, and Shuangmei Liu are Joint first authors.
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Tu, G., Zou, L., Liu, S. et al. Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia. Purinergic Signalling 12, 521–535 (2016). https://doi.org/10.1007/s11302-016-9518-3
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DOI: https://doi.org/10.1007/s11302-016-9518-3