期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 93, 期 -, 页码 18-31出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2016.02.002
关键词
Endotoxemia; Cardiac function; Adiponectin; Apoptosis; Autophagy; Inflammation
资金
- NIH/NIGMS [8P20GM103432]
- National Natural Science Foundation of China [NSFC81570225]
Background: Adiponectin (APN), an adipose-derived adipokine, alleviates lipopolysaccharide (LPS)-induced injury in multiple organs including hearts although the underlying mechanism in endotoxemia remains elusive. This study was designed to examine the role of adiponectin in LPS-induced cardiac anomalies and inflammation as well as the underlying mechanism with a focus on autophagy a conserved machinery for bulk degradation of intracellular components. Methods and results: Wild-type (WT) and APN(-/-) mice were challenged with LPS (4 mg/kg) or saline for 6 h. Echocardiography, cardiomyocyte contractile and intracellular Ca2+ properties were evaluated. Markers of autophagy, apoptosis and inflammation including LOB, p62, Beclin1, AMPK, mTOR, ULK, Caspase 3, Bcl-2, Bax, TLR4, TRAF6, MyD88, IL-1B, TNF alpha, HMGB1, JNK and I kappa B were examined using Western blot or RT-PCR. Our results showed that LPS challenge reduced fractional shortening, compromised cardiomyocyte contractile capacity, intracellular Ca2+ handling properties, apoptosis and inflammation, which were accentuated by adiponectin ablation. Adiponectin ablation unmasked the LPS-induced cardiac remodeling (left ventricular end systolic diameter) and prolongation of cell shortening. The detrimental effects of adiponectin ablation were associated with dampened autophagy in response to LPS through an AMPK-mTOR-ULK1-dependent mechanism. In vivo administration of AMPK activator AICAR or the autophagy inducer rapamycin effectively attenuated or obliterated LPS-induced and adiponectin deficiency-accentuated responses without affecting TLR4, TRAF6 and MyD88. Conclusions: The findings suggest that AMPK and autophagy may play a permissive role in the adiponectin deficiency-exacerbated cardiac dysfunction, apoptosis and inflammation under LPS challenge possibly at the post-TLR4 receptor level. (C) 2016 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据