Cardioprotective natural compound pinocembrin prevents acute ischemic
myocardial injury through enhancing glycolysis
Abstract
Background and Purpose: Emerging evidence has shown that pinocembrin
protects myocardial from ischemic injury in animals. However, it is
unknown whether it has cardioprotection when given at the onset of
reperfusion. Also, mechanisms mediating the cardioprotective actions of
pinocembrin were largely unknown. Thus, this study aimed to investigate
the effects of pinocembrin postconditioning on ischemia-reperfusion
(I/R) injury and the underlying mechanisms. Experimental Approach: In
vivo mouse model of myocardial I/R injury, ex vivo isolated rat heart
with global I/R and in vitro hypoxia/reoxygenation (H/R) injury model
for primary cardiomyocytes were used. Key Results: We found that
pinocembrin postconditioning significantly reduced the infarct size and
improved cardiac contractile function after acute myocardial I/R.
Mechanically, in primary cardiomyocytes we found that pinocembrin may
confer protection in part via direct stimulation of cardiac glycolysis
via promoting the expression of glycolytic enzyme, PFKFB3. Besides,
PFKFB3 inhibition abolished pinocembrin-induced glycolysis and
protection in cardiomyocytes. More importantly, PFKFB3 knockdown via
cardiotropic adeno-associated virus (AAV) abrogated cardioprotective
effects of pinocembrin. Conclusions and Implications: In conclusion,
these results established that the acute cardioprotective benefits of
pinocembrin are mediated in part via glycolytic stimulation through
PFKFB3, which may provide a new therapeutic target to impede the
progression of myocardial I/R injury.