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Sodium tanshinone IIA sulfonate ameliorates ischemia-induced myocardial inflammation and lipid accumulation in Beagle dogs through NLRP3 inflammasome.

Abstract：

BACKGROUND:The activation of NOD-like receptor (NLR) family, pyrin-domain containing 3 (NLRP3) inflammasome has now been proven to have a close connection with myocardial ischemia (MI) during acute phase, but the mechanisms are not completely clear. This study investigated the role of NLRP3 inflammasome in pathogenesis of MI injury including inflammation and lipid accumulation, as well as the effects of sodium tanshinone IIA sulfonate (STS) and diltiazem hydrochloride (DI). METHODS:Occlusion of left anterior descending (LAD) in canines was employed to induce MI. STS and DI were given intravenously 15 min after LAD occlusion. Cardiac function, inflammation and lipid levels, as well as related signaling pathways were determined. RESULTS:MI induced in Beagle dog was characterized by elevated ST-segment and increased CK-MB level in serum. Cardiac NLRP3 inflammasome was activated with elevated myocardial IL-1β and IL-18 concentrations mediated by ROS over-production and TXNIP over-expression in MI dogs. Additionally, pro-inflammatory cytokines induced impairment of cardiac JAK2-STAT3 inflammatory pathway and insulin signaling pathway in this model, resulting in down-regulation of cardiac PPAR-α expression, subsequently causing lipid metabolism disorders characterized by elevation of myocardial lipid concentrations. These abnormalities were attenuated by the treatment of STS and DI. CONCLUSIONS:These data firstly demonstrated that cardiac NLRP3 inflammasome activation driven by cardiac ROS over-production and TXNIP up-expression resulted in impairment of the JAK2-STAT3 and insulin signaling pathways, leading to disorder of lipid metabolism in myocardial ischemic dogs through PPAR-α over-expression. STS and DI might target cardiac NLRP3 inflammasome in preventing MI injury.

journal_name

Int J Cardiol

journal_title

International journal of cardiology

authors

Hu Q,Wei B,Wei L,Hua K,Yu X,Li H,Ji H

doi

10.1016/j.ijcard.2015.05.152

subject

Has Abstract

pub_date

2015-10-01 00:00:00

pages

183-92

eissn

0167-5273

issn

1874-1754

pii

S0167-5273(15)01236-X

journal_volume

196

pub_type

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Sodium tanshinone IIA sulfonate ameliorates ischemia-induced myocardial inflammation and lipid accumulation in Beagle dogs through NLRP3 inflammasome.