Abstract | BACKGROUND: Myocardial mitochondrial dysfunction is the leading cause of chronic heart failure (CHF). Increased reactive oxygen species (ROS) levels, disruption of mitochondrial biogenesis and mitochondrial Ca2+([Ca2+]m) homeostasis and reduction of the mitochondrial membrane potential (ΔΨm) cause myocardial mitochondrial dysfunction. Therefore, treating CHF by targeting mitochondrial function is a focus of current research. For the first time, this study investigated the effects of the strong antioxidant pyrroloquinoline quinone (PQQ) on mitochondrial function in a cardiac pressure overload model, and the mechanism by which PQQ regulates [Ca2+]m homeostasis was explored in depth. METHODS: RESULTS: In vivo and in vitro, PQQ pretreatment improved pressure overload-induced cardiac remodelling and cell hypertrophy, thus preventing the occurrence of CHF. PQQ also prevented mitochondrial morphology damage and reduced the PGC-1α and TFAM downregulation caused by TAC or Ang II. In addition, in NRVMs treated with Ang II + PQQ, PQQ regulated ROS levels and increased the ΔΨm. PQQ also regulated [Ca2+]m homeostasis and prohibited [Ca2+]m overloading by increasing NCLX expression. CONCLUSIONS: These results show that PQQ can prevent [Ca2+]m overload by increasing NCLX expression and thereby reducing ROS production and protecting the ΔΨm. At the same time, PQQ can increase PGC-1α and TFAM expression to regulate mitochondrial biogenesis. These factors can prevent mitochondrial dysfunction, thereby reducing cardiac damage caused by pressure overload and preventing the occurrence of CHF.
|
Authors | Xuan Xu, Chu Chen, Wen-Jiang Lu, Yi-Ling Su, Jia-Yu Shi, Yu-Chen Liu, Li Wang, Chen-Xi Xiao, Xiang Wu, Qi Lu |
Journal | Cardiovascular diagnosis and therapy
(Cardiovasc Diagn Ther)
Vol. 10
Issue 3
Pg. 453-469
(Jun 2020)
ISSN: 2223-3652 [Print] China |
PMID | 32695625
(Publication Type: Journal Article)
|
Copyright | 2020 Cardiovascular Diagnosis and Therapy. All rights reserved. |