| Autor: |
Gao, Hongmei, Yin, Jie, Shi, Yugen, Hu, Hesheng, Li, Xiaolu, Xue, Mei, Cheng, Wenjuan, Wang, Ye, Li, Xinran, Li, Yongkang, Wang, Yu, Yan, Suhua |
| Předmět: |
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| Zdroj: |
Cardiovascular Therapeutics; Apr2017, Vol. 35 Issue 2, pn/a-N.PAG, 11p |
| Abstrakt: |
Background Inflammation-dominated sympathetic sprouting adjacent to the necrotic region following myocardial infarction (MI) has been implicated in the etiology of arrhythmias resulting in sudden cardiac death; however, the mechanisms responsible remain to be elucidated. Although P2X7R is a key immune mediator, its role has yet to be explored. Objective We investigated whether P2X7R regulates NF-κB and affects cardiac sympathetic reinnervation in rats undergoing MI. Methods and Results An adenoviral vector with a short hairpin RNA (shRNA) sequence inserted was adopted for the inhibition of P2X7R in vivo. Myocardial infarction was induced by left coronary artery ligation, and immediately after that, recombinant P2X7R-shRNA adenovirus, negative adenovirus (control), or normal saline solution (vehicle) was injected intramyocardially around the MI region and border areas. A high level of P2X7R was activated in the infarcted tissue at an early stage. The administration of P2X7R RNAi resulted in the inhibition of Akt and Erk1/2 phosphorylation and decreased the activation of NF-κB and macrophage infiltration, as well as attenuated the expression of nerve growth factor (NGF). Eventually, the NGF-induced sympathetic hyperinnervation was blunted, as assessed by the immunofluorescence of tyrosine hydroxylase (TH) and growth-associated protein 43 (GAP 43). At 7 days post-MI, the arrhythmia score of programmed electrical stimulation in the vehicle-treated infarcted rats was higher than the MI-shRNA group. Further amelioration of cardiac dysfunction was also detected. Conclusions The administration of P2X7R RNAi during the acute inflammatory response phase prevented the process of sympathetic hyperinnervation after MI, which was associated in part with inhibiting the Akt and ERK1/2 pathways and NF-κB activation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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