NLRP3 Inflammasome as a Molecular Marker in Diabetic Cardiomyopathy.

Beibei Luo,Weiqiang Huang,Zhiyu Zeng,Feng Huang,Yiying Liang,Yanli Liu,Yan He,Honghong Ke,Zhe Wei

doi:10.3389/fphys.2017.00519

Abstract

Diabetic cardiomyopathy (DCM), a common consequence of longstanding diabetes mellitus, is initiated by death of cardiomyocyte. Hyperglycemia-induced reactive oxygen species (ROS) overproduction is a major contributor of the chronic low-grade inflammation that characterizes as the DCM. ROS may promote the activation of nucleotide-binding oligomerization domain like receptor (NLR) pyrin domain containing 3 (NLRP3) inflammasome, a novel regulator of inflammation and cell death, by nuclear factor-kB (NF-κB) and thioredoxin interacting/inhibiting protein (TXNIP). NLRP3 inflammasome regulates the death of cardiomyocyte and activation of fibroblast in DCM, which is involved in the structural and functional disorder of DCM. However, comprehensive understanding of molecular mechanisms linking NLRP3 inflammasome and disorder of cardiomyocyte and fibroblast in DCM is lacking. Here, we review the molecular mechanism(s) of NLRP3 inflammasome activation in response to hyperglycemia in DCM.

Highlights

Diabetic cardiomyopathy (DCM), one of the severe complication of diabetes mellitus, is the leading cause of death in diabetes patients (Shaw et al, 2010)
A growing list of molecules has been examined as possible molecular markers for heart failure (HF) and cardiovascular disease (CVD), exemplified by the myocyte injury markers troponins I and T, the myocyte stress markers Brain natriuretic peptide (BNP) and ST2/IL-33, and the inflammation markers C-reactive protein (CRP) and certain cytokines (TNF, IL-1β, and IL18; Braunwald, 2008)
We found that the protective effect of the anti-inflammation drug rosuvastatin (RSV) was associated with its ability to inhibit the activation of NLRP3 inflammasome via thioredoxin interacting/inhibiting protein (TXNIP) and suppress the phosphorylation of MAPK signal pathways in DCM (Luo et al, 2014a)

Summary

Introduction

Diabetic cardiomyopathy (DCM), one of the severe complication of diabetes mellitus, is the leading cause of death in diabetes patients (Shaw et al, 2010). We found that the protective effect of the anti-inflammation drug rosuvastatin (RSV) was associated with its ability to inhibit the activation of NLRP3 inflammasome via TXNIP and suppress the phosphorylation of MAPK signal pathways in DCM (Luo et al, 2014a). The activated caspase-1 has two major functions: the regulated function that processes pro-IL-18 and pro-IL-1β into their mature forms (IL-18 and IL-1β) and the novel function that induces pyroptosis.

Results

Conclusion