NLRP3 Inflammasome/Pyroptosis: A Key Driving Force in Diabetic Cardiomyopathy

Abstract

Diabetic cardiomyopathy (DCM), a serious diabetic complication, is a kind of low-grade inflammatory cardiovascular disorder. Due to the high risk of morbidity and mortality, DCM has demanded the attention of medical researchers worldwide. The pathophysiological nature of DCM is intricate, and the genesis and development of which are a consequence of the coaction of many factors. However, the exact pathogenesis mechanism of DCM remains unclear. Pyroptosis is a newly identified programmed cell death (PCD) that is directly related to gasdermin D(GSDMD). It is characterized by pore formation on the cell plasma membrane, the release of inflammatory mediators, and cell lysis. The initiation of pyroptosis is closely correlated with NOD-like receptor 3 (NLRP3) activation, which activates caspase-1 and promotes the cleaving of GSDMD. In addition to adjusting the host’s immune defense, NLRP3 inflammasome/pyroptosis plays a critical role in controlling the systemic inflammatory response. Recent evidence has indicated that NLRP3 inflammasome/pyroptosis has a strong link with DCM. Targeting the activation of NLRP3 inflammasome or pyroptosis may be a hopeful therapeutic strategy for DCM. The focus of this review is to summarize the relevant mechanisms of pyroptosis and the relative contributions in DCM, highlighting the potential therapeutic targets in this field.

Cardiometabolic Care: Assessing Patients with Diabetes Mellitus with No Overt Cardiovascular Disease in the Light of Heart Failure Development Risk

“…Similarly, AGEs impair endothelial NO production and predisposes to concentric LV remodeling and myocardial stiffness as observed in diabetic cardiomyopathy patients with HFpEF [ 8 , 12 ]. In addition, in T2DM there is an increase in glucose autooxidation and free fatty acid concentrations, which can create oxidative stress in the myocardium and consequently induce concentric ventricular remodeling [ 3 ].…”

“…The effects of this pathological entity on cardiovascular health (CV) create further public health challenges and remain responsible for the increased prevalence of cardiovascular disease (CVD) [ 1 ]. Beyond coronary artery disease (CAD) progression, DM can precipitate or worsen heart failure (HF) due to multifactorial mechanisms (i.e., the accumulation of advanced glycation end products (AGEs), oxidative stress, inflammatory status impairment, decay of intracellular calcium, changes in microRNAs expression) [ 2 , 3 , 4 ]. Patients with diabetes develop HF at more than two-times the rate of patients without diabetes [ 1 ].…”

Crosstalk of NLRP3 inflammasome and noncoding RNAs in cardiomyopathies

“…The possible diagnostic and prognostic biomarkers for cardiomyopathies include the deregulation of NLRP3 inflammasome and ncRNAs. The NLRP3 inflammasome has been suggested as a potential molecular marker in the context of diabetic cardiomyopathy 127 . Moreover, it has been documented that some miRNAs and lncRNAs exhibit dysregulation as a consequence of aging, resulting in alterations within the cardiovascular system 128 .…”

“…For instance, several drugs have been discovered to have good promise for the therapy of diabetic cardiomyopathy by targeting the NLRP3 inflammasome or pyroptosis (Table 2). 127 Furthermore, the proposition of targeting specific miRNAs and lncRNAs has emerged as a viable therapeutic approach in the management of cardiomyopathies 128…”

“…The NLRP3 inflammasome has been suggested as a potential molecular marker in the context of diabetic cardiomyopathy. 127 Moreover, it has been documented that some miRNAs and lncRNAs exhibit dysregulation as a consequence of aging, resulting in alterations within the cardiovascular system. 128 Hence, the discernment of distinct constituents of the NLRP3 inflammasome and ncRNAs may offer fresh perspectives into the molecular mechanisms that underlie cardiomyopathies, and potentially facilitate the advancement of innovative diagnostic and prognostic approaches.…”