Abstract | PURPOSE:
Diabetic 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. METHODS: Diabetes 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. RESULTS: CONCLUSION: PQQ 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. Diagram 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.
|
Authors | Xue-Feng Qu, Bing-Zhong Zhai, Wen-Li Hu, Min-Han Lou, Yi-Hao Chen, Yi-Feng Liu, Jian-Guo Chen, Song Mei, Zhen-Qiang You, Zhen Liu, Li-Jing Zhang, Yong-Hui Zhang, Yin Wang |
Journal | European journal of nutrition
(Eur J Nutr)
Vol. 61
Issue 4
Pg. 1823-1836
(Jun 2022)
ISSN: 1436-6215 [Electronic] Germany |
PMID | 34997266
(Publication Type: Journal Article)
|
Copyright | © 2021. The Author(s). |
Chemical References |
- Inflammasomes
- NF-kappa B
- NLR Family, Pyrin Domain-Containing 3 Protein
- PQQ Cofactor
- Glucose
|
Topics |
- Animals
- Cardiomegaly
- Diabetes Mellitus, Experimental
(complications)
- Diabetic Cardiomyopathies
(drug therapy, etiology, metabolism)
- Fibrosis
- Glucose
- Inflammasomes
(metabolism)
- Inflammation
(complications)
- Mice
- Mice, Inbred C57BL
- NF-kappa B
(metabolism)
- NLR Family, Pyrin Domain-Containing 3 Protein
(metabolism)
- PQQ Cofactor
(metabolism, pharmacology, therapeutic use)
- Pyroptosis
- Signal Transduction
|