Though early reperfusion during myocardial infarction is essential for saving the myocardium, lethal reperfusion injury occurs and contributes to cardiac dysfunction and infarction. Ischaemic preconditioning and postconditioning (repetitive short period of I/R applied during early reperfusion, PoC) are both protective strategy by showing the attenuation of lethal reperfusion injury. Meanwhile several pharmacological interference during late infarction, immediately prior to reperfusion or at the onset of reperfusion have been tested. This approach is more clinically feasible than mechanical PoC, while so far limit agents are clinically available for the patient with ischaemic heart disease.
Recently a team of researchers, led by Prof. YANG Huangtian, at the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, found that berbamine (a natural small-molecule compound, derived from the roots, barks and stems of Barberry) confer cardioprotective effects when given at the onset of reperfusion (berbamine PoC, BMPoC), an approach with more clinical impact. The researchers revealed that BMPoC reversed I/R-impaired autophagic flux via suppressing Beclin 1 expression. In vivo downregulation of Beclin 1 mimic the cardioprotection of BMPoC with improved autophagic flux and reduced infarct size. The study further confirmed that the activated PI3K/Akt pathway contributes to the BMPoC-afforded cardioprotection by modulating autophagy. The results demonstrate that BMPoC significantly improves left ventricular functional recovery and limits infarct size. Such cardioprotection is at least partially mediated by the suppression of I/R-induced Beclin 1 expression and recovery of I/R-impaired autophagosome processing through the activation of PI3K/Akt signaling pathways.
These findings not only reveal the potential therapeutic value of berbamine in the protection of myocardium from ischaemia disease but also provide new insight to the understanding of molecular mechanisms of postconditioning.
This study was published online in Cell Death and Disease on Feb 2, 2017. This study was supported by National Science and Technology Major Project of China and Natural Science Foundation of Shanghai.
Prof. YANG Huang-Tian
Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
320 Yueyang Road, Shanghai 200031, China.