Abstract
PurposeDiabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism.MethodsDiabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h.ResultsPQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy—(ANP and BNP), myocardial fibrosis—(collagen I and TGF-β1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions.ConclusionPQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM.Graphical abstractDiagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1β, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.
Highlights
Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes mellitus and is the leading cause of mortality in diabetic patients [1]
The mice were randomly divided into the following five groups (n = 10 for each group): controls (Ctl), diabetic cardiomyopathy (DCM), diabetic mice treated with a low dose of Pyrroloquinoline quinone (PQQ) (DCM + PQQL), diabetic mice treated with a medium dose of PQQ (DCM + PQQM), and diabetic mice treated with a high dose of PQQ (DCM + PQQH)
To further determine the effects of PQQ on cardiac fibrosis, we examined the levels of fibrosis-related mRNAs, including collagen I (Col I), collagen III (Col III), transforming growth factor-β1 (TGF-β1), and connective tissue growth factor (CTGF)
Summary
Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes mellitus and is the leading cause of mortality in diabetic patients [1]. Structural and functional abnormalities are the main features of DCM, which is characterized by myocardial hypertrophy, cardiac fibrosis, and cardiac dysfunction [2]. The pathogenesis of DCM includes mitochondrial dysfunction, inflammation, extracellular matrix deposition, and cell death [3]. The inflammatory response has been shown to play an important role in the pathophysiology of DCM [4, 5]. Bioactive substances in food have important protective effects against cardiac diseases via anti-inflammatory and anti-oxidative effects. The use of appropriate bioactive substances combined with clinical treatment may be an effective method for DCM management
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
