PFKFB3 exacerbates myocardial injury by accelerating CXCR4 hi neutrophil mobilization after acute myocardial infarction
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
This article is not in any list yet, why not save it to one of your lists.Abstract
Background
CXCR4 hi neutrophil mobilization is a key cause of myocardial damage after acute myocardial infarction (AMI). 6-Phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, plays a crucial role in regulating neutrophil function. However, researchers have not clearly determined whether PFKFB3 is involved in AMI-induced CXCR4 hi neutrophil mobilization.
Methods
First, the circulating CXCR4 hi neutrophil percentage and neutrophil Pfkfb3 mRNA expression were measured in AMI patients and left anterior descending coronary artery (LADCA)-ligated mice. Next, we explored the relationship between PFKFB3 and CXCR4 expression in lipopolysaccharide (LPS)-stimulated cell models. Neu-PFKFB3 −/− mice were used to investigate the effect of conditional knockout of the Pfkfb3 gene in neutrophils on AMI-induced myocardial inflammatory injury.
Results
In AMI patients, the expression level of Pfkfb 3 gene was markedly regulated in AMI-induced neutrophils and was positively related to the content of plasma inflammatory factors in AMI patients. Further study revealed that PFKFB3 promotes CXCR4 hi neutrophil mobilization by reprogramming glycolytic metabolism and subsequently exacerbates inflammatory injury in the myocardial tissues of AMI model mice. However, specific knockout of Pfkfb3 gene in neutrophils protects mice from AMI-induced myocardial inflammatory injury by inhibiting the mobilization of CXCR4 hi neutrophils.
Conclusion
PFKFB3 exacerbates AMI-induced myocardial inflammatory injury by accelerating CXCR4 hi neutrophil mobilization. The mechanism involves PFKFB3-mediated reprogramming of glycolytic metabolism.
