Involvement of pyroptosis pathway in epicardial adipose tissue- myocardium axis in experimental heart failure with preserved ejection fraction

作者全名："Xia, Yi-Yuan; Shi, Yi; Li, Zheng; Li, Hui; Wu, Li-Da; Zhou, Wen-Ying; Gu, Yue; Ling, Zhi-Yu; Zhang, Jun-Xia; Chen, Shao-Liang"

作者地址："[Xia, Yi-Yuan; Shi, Yi; Li, Zheng; Li, Hui; Wu, Li-Da; Zhou, Wen-Ying; Gu, Yue; Zhang, Jun-Xia; Chen, Shao-Liang] Nanjing Med Univ, Nanjing Hosp 1, Dept Cardiol, Nanjing, Jiangsu, Peoples R China; [Ling, Zhi-Yu] Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 2, Chongqing, Peoples R China; [Gu, Yue] Nanjing Med Univ, Collaborat Innovat Ctr Cardiovasc Dis Translat Med, Key Lab Targeted Intervent Cardiovasc Dis, Nanjing, Peoples R China; [Zhang, Jun-Xia; Chen, Shao-Liang] Nanjing Med Univ, Nanjing Hosp 1, Dept Cardiol, Nanjing 210006, Jiangsu, Peoples R China"

通信作者："Ling, ZY (通讯作者)，Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 2, Chongqing, Peoples R China.; Zhang, JX; Chen, SL (通讯作者)，Nanjing Med Univ, Nanjing Hosp 1, Dept Cardiol, Nanjing 210006, Jiangsu, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000904608400007

JCR分区：Q2

影响因子：3.1

年份：2022

卷号：636

期号：　

开始页：62

结束页：70

文献类型：Article

关键词：Heart failure with preserved ejection; fraction; Epicardial adipose tissue; Epicardial adipose tissue-myocardium axis; Inflammation; Pyroptosis

摘要："Epicardial adipose tissue (EAT) is a metabolically active organ which generates inflammatory cytokines. Thickness of EAT is associated with onset and development of heart failure with preserved ejection fraction (HFpEF). However, it is still unclear the specific mechanisms and pharmacological targets on EAT induced inflammation in HFpEF. A two-hit protocol with western diet and Nu-nitrol-arginine methyl ester (L-NAME) was used to establish HFpEF mouse model. In HFpEF mice, inflammatory biomarkers, such as tumor necrosis factor (TNF)-a, interleukin (IL)-1b and von willebrand factor (vWF) elevated in myocardium compared to control. Inflammatory cell infiltration in myocardium was increased. In HFpEF mice, inflammasome-mediated pyroptosis pathway was activated in the EAT. Suppression of pyroptosis-related protein gasdermin D (GSDMD) in cultured EAT could lower cardiomyocyte inflammation and autophagy. Furthermore, spironolactone and rosuvastatin, the two-hit anti-inflammatory agents, reduced NLR family pyrin domain containing 3 (NLRP3)/GSDMD pyroptosis in EAT and autophagy in myocardium of HFpEF mouse. The combination treatment also enhanced exercise tolerance and appeased inflammatory injuries in HFpEF mice. Conclusion: Pyroptosis signaling is involved in EAT-myocardium axis in mouse model of HFpEF. Targeting adipocyte-derived inflammation in EAT bears potential to treatment HFpEF. (c) 2022 Elsevier Inc. All rights reserved."

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