The Role of NLRP3 Inflammasome in Diabetic Cardiomyopathy and Its Therapeutic Implications

Abstract

Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus (DM). However, the precise molecular mechanisms remain largely unclear, and it is still a challenging disease to diagnose and treat. The nucleotide-binding oligomerization domain and leucine-rich repeat pyrin 3 domain (NLRP3) inflammasome is a critical part of the innate immune system in the host to defend against endogenous danger and pathogenic microbial infections. Dysregulated NLRP3 inflammasome activation results in the overproduction of cytokines, primarily IL-1β and IL-18, and eventually, inflammatory cell death-pyroptosis. A series of studies have indicated that NLRP3 inflammasome activation participates in the development of DCM, and that corresponding interventions could mitigate disease progression. Accordingly, this narrative review is aimed at briefly summarizing the cell-specific role of the NLRP3 inflammasome in DCM and provides novel insights into developing DCM therapeutic strategies targeting the NLRP3 inflammasome.

Effects of the S1P/S1PR1 signaling pathway on high glucose-induced NRK-52E epithelial- mesenchymal transdifferentiation via regulation of ROS/NLRP3

“…In the meantime, the inflammatory response is another crucial sign of DN, and the NLRP3 inflammasome is crucial to the DN pathogenesis [40,41], persistent HG conditions can enable the NLRP3 inflammasome [42,43]. Therefore, treatment of DN can be achieved by inhibiting NLRP3 inflammasome.…”

Crosstalk of NLRP3 inflammasome and noncoding RNAs in cardiomyopathies

“…While recent articles have provided valuable insights into the role of NLRP3 inflammasome in cardiomyopathy, several areas remain to be explored. Further research is required to clarify the upstream triggers and signaling pathways regulating activation of NLRP3 inflammasome in various types of cardiomyopathies 85 . Furthermore, more investigations are warranted to evaluate the clinical efficacy and safety of pharmacological agents targeting NLRP3 inflammasome in human patients (Table 2).…”

“…The involvement of the NLRP3 inflammasome and ncRNAs has been suggested in the development of cardiomyopathies, and these findings may have significant implications for diagnostic and prognostic purposes. As an illustration, the upregulation of NLRP3, ASC, caspase‐1, and IL‐1β is observed in a model of type 2 diabetes induced by streptozotocin (STZ) in conjunction with a high‐fat diet 85 . Moreover, it has been demonstrated that the activation of the NLRP3 inflammasome contributes to the development of cardiomyopathies and atrial fibrillation 126 .…”

“…79 The occurrence of cardiac inflammation can be initiated by a range of factors, such as infections, toxins, or myocardial infarction. 82 85 Furthermore, more investigations are warranted to evaluate the clinical efficacy and safety of pharmacological agents targeting NLRP3 inflammasome in human patients (Table 2).…”

“…As an illustration, the upregulation of NLRP3, ASC, caspase-1, and IL-1β is observed in a model of type 2 diabetes induced by streptozotocin (STZ) in conjunction with a high-fat diet. 85 Moreover, it has been demonstrated that the activation of the NLRP3 inflammasome contributes to the development of cardiomyopathies and atrial fibrillation. 126 There have been reports indicating an association between dysregulated ncRNAs and cardiomyopathies, such as ischemic heart failure and dilated cardiomyopathy.…”