Open AccessMicroglial Mincle receptor in the PVN contributes to sympathetic hyperactivity in acute myocardial infarction rat
Author(s) -
Wang Yu,
Yin Jie,
Wang Cailing,
Hu Hesheng,
Li Xiaolu,
Xue Mei,
Liu Ju,
Cheng Wenjuan,
Wang Ye,
Li Yan,
Shi Yugen,
Tan Jiayu,
Li Xinran,
Liu Fuhong,
Liu Qiang,
Yan Suhua
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13890
Subject(s) - medicine , receptor , sympathetic nervous system , endocrinology , myocardial infarction , inflammasome , blood pressure
Malignant ventricular arrhythmias ( VA s) following myocardial infarction ( MI ) is a lethal complication resulting from sympathetic nerve hyperactivity. Numerous evidence have shown that inflammation within the paraventricular nucleus ( PVN ) participates in sympathetic hyperactivity. Our aim was to explore the role of Macrophage‐inducible C‐type lectin (Mincle) within the PVN in augmenting sympathetic activity following MI ,and whether NOD ‐like receptor family pyrin domain‐containing 3 ( NLRP 3) inflammasome/ IL ‐1β axis is involved in this activity. MI was induced by coronary artery ligation. Mincle expression localized in microglia within the PVN was markedly increased at 24 hours post‐ MI together with sympathetic hyperactivity, as indicated by measurement of the renal sympathetic nerve activity ( RSNA ) and norepinephrine ( NE ) concentration. Mincle‐specific si RNA was administrated locally to the PVN , which consequently decreased microglial activation and sympathetic nerve activity. The MI rats exhibited a higher arrhythmia score after programmed electric stimulation than that treated with Mincle si RNA , suggesting that the inhibition of Mincle attenuated foetal ventricular arrhythmias post‐ MI . The underlying mechanism of Mincle in sympathetic hyperactivity was investigated in lipopolysaccharide ( LPS )‐primed naïve rats. Recombinant Sin3A‐associated protein 130kD ( rSAP 130), an endogenous ligand for Mincle, induced high levels of NLRP 3 and mature IL ‐1β protein. PVN ‐targeted injection of NLRP 3 si RNA or IL ‐1β antagonist gevokizumab attenuated sympathetic hyperactivity. Together, the data indicated that the knockdown of Mincle in microglia within the PVN prevents VA s by attenuating sympathetic hyperactivity and ventricular susceptibility, in part by inhibiting its downstream NLRP 3/ IL ‐1β axis following MI . Therapeutic interventions targeting Mincle signalling pathway could constitute a novel approach for preventing infarction injury.