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

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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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Correspondence to Guilin Li or Shangdong Liang.

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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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