Rosuvastatin Alleviates Diabetic Cardiomyopathy by Inhibiting NLRP3 Inflammasome and MAPK Pathways in a Type 2 Diabetes Rat Model

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• 作者：Beibei Luo (1)
  Bo Li (1)
  Wenke Wang (1)
  Xiangjuan Liu (1)
  Xiaoman Liu (1)
  Yanfei Xia (1)
  Cheng Zhang (1)
  Yun Zhang (1)
  Mingxiang Zhang (1)
  Fengshuang An (1)
  
• 关键词：DCM ; Rosuvastatin ; NLRP3 inflammasome ; Gene silencing ; MAPKs
• 刊名：Cardiovascular Drugs and Therapy
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：28
• 期：1
• 页码：33-43
• 全文大小：1,117 KB
• 作者单位：Beibei Luo (1)
  Bo Li (1)
  Wenke Wang (1)
  Xiangjuan Liu (1)
  Xiaoman Liu (1)
  Yanfei Xia (1)
  Cheng Zhang (1)
  Yun Zhang (1)
  Mingxiang Zhang (1)
  Fengshuang An (1)
  
  1. The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, No.107, Wen Hua Xi Road, Jinan, Shandong, 250012, People’s Republic of China
  
• ISSN：1573-7241

文摘

Purpose Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is important in inflammation of several diabetic complications. However, the potential role of NLRP3 inflammasome in the inflammatory process of diabetic cardiomyopathy (DCM) remains unclear. Although rosuvastatin (RSV) has an anti-inflammatory effect on some cardiovascular diseases, its influence on DCM is incompletely understood. We aimed to explore the effect on and underlying mechanism of RSV in DCM, and whether NLRP3 is a target for RSV. Methods Type 2 diabetes was induced in rat. The characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. The expression of factors was determined by real-time RT-PCR and western blot. Eight-week RSV treatment and NLRP3 gene silencing were used to investigate the effect and underlying target of RSV in DCM. Results Compared with controls, diabetic rats showed severe metabolic disorder, cardiac dysfunction, fibrosis, disorganized ultrastructure, and excessive activation of thioredoxin interacting/inhibiting protein (TXNIP, p-lt;-.05), NLRP3 inflammasome (NLRP3, p-lt;-.01; apoptosis-associated speck-like protein containing a caspase recruitment domain [ASC], p-lt;-.05; caspase-1, p-lt;-.01), interleukin-1β (p-lt;-.01) and mitogen-activated protein kinases (MAPKs, all p-lt;-.01). Compared with diabetes alone, RSV ameliorated the overexpression of NLRP3 inflammasome (NLRP3, p-lt;-.05; ASC, p-lt;-.05; pro-caspase-1 p-lt;-.05, caspase-1 p20, p-lt;-.01) and MAPKs (all p-lt;-.05), which paralleled the cardiac protection of RSV. Silencing NLRP3 ameliorated cardiac remodeling and dysfunction. The beneficial effects of RSV in vehicle-treated rats were all abrogated in NLRP3-silenced rats. Conclusions The beneficial effect of RSV on DCM depended on inhibited NLRP3 inflammasome, and correlated with suppression of the MAPKs.