The NLRP3 Inflammasome and Diabetic Cardiomyopathy
Editorial to: “Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model” by Beibei Luo et al.
Chronic hyperglycemia and dyslipidemia are primarily linked to various complications of diabetes, especially of type 2. Diabetes mellitus, both type 1 and 2, accompanies cellular oxidative/nitrosative stress and insulin resistance/deficiency leading to generation of a chronic low-grade inflammatory environment within tissues. Recent studies have focused on the role of a protein platform called the NLRP3 inflammasome ((nucleotide-binding domain, leucine-rich repeats containing family, pyrin domain-containing-3 (NLRP3), its adaptor apoptotic speck protein containing a caspase recruitment domain (ASC) and pro-caspase-1)), which activates caspase-1 and interleukin-1beta (IL-1β) [1‐3]. Among the various inflammasomes, NLRP3 is widely activated in sterile inflammation (inflammation not involving infection) and is the most studied inflammasome. IL-1β is a highly inflammatory cytokine; therefore, its activity is regulated at multiple steps, including priming (expression), processing (activation) and exocytosis (release) [4]. Subsequently, pro-inflammatory IL-1β acts on its surface receptor, IL-1R, which may activate its own expression and other inflammatory cytokines generating reactive oxygen/nitrogen species (ROS/RNS) and cellular stress. IL-1β itself may propagate a feed forward loop maintaining chronic ROS/RNS stress, inflammation and premature cell death and disease progression of diabetes, including diabetic cardiomyopathy (DCM) (Fig. 1). As mentioned above, the NLRP3 inflammasome is considered as a sensor of cellular stress induced by various extrinsic (bacteria, virus, toxins, UV, and others) and intrinsic (metabolic imbalance, mitochondrial and endoplasmic reticulum stresses, organelle damage and oxidative stress) agents. Therefore, understanding the molecular mechanism(s) of the NLRP3 inflammasome assembly and activation is critical and currently constitutes an area of intense research in chronic metabolic diseases such as diabetes and obesity.
×
…
Anzeige
Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten
The NLRP3 Inflammasome and Diabetic Cardiomyopathy Editorial to: “Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model” by Beibei Luo et al.