Cardioprotective effect of IGF-1 against myocardial ischemia/reperfusion injury through activation of PI3K/Akt pathway in rats in vivo

Abstract

Objective It remains unknown whether insulin-like growth factor-1 (IGF-1) can attenuate myocardial ischemia/reperfusion (I/R) injury in vivo by activating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway. This study investigated the possible interaction of IGF-1 with the PI3K/Akt pathway in cardioprotection against in vivo myocardial I/R injury in rats. Methods We established a myocardial I/R model in rats through left anterior descending artery ligation for 40 minutes followed by 6 hours reperfusion. The PI3K/Akt inhibitor, LY294002 (0.3 mg/kg), was injected through the caudal vein 30 minutes before myocardial ischemia, and IGF-1 (1 µg/kg or 5 µg/kg) was injected through the caudal vein 10 minutes before myocardial ischemia. Results IGF-1 treatment decreased myocardial infarct size; myocardial cell apoptosis; and serum lactate dehydrogenase, creatine kinase MB, and cardiac troponin I levels in rats with myocardial I/R in vivo. Moreover, IGF-1 treatment led to significant increases in expression levels of p-Akt (Ser473) and B cell lymphoma 2, while reducing expression levels of caspase-9 mRNA and cleaved caspase-9 protein in rats with myocardial I/R. However, pretreatment with LY294002 significantly reduced the cardioprotective effects of IGF-1. Conclusion Treatment with IGF-1 may confer cardiac protection against in vivo myocardial I/R injury via the PI3K/Akt pathway in rats.

Insulin-like growth factor-1 short-period therapy improves cardiomyopathy stimulating cardiac progenitor cells survival in obese mice

“…This pathological scenario is related to the observed reduction of pAkt/Akt ratio in OG. After IGF-1 therapy apoptosis levels were reduced in OG þ IGF-1 through PI3K/ Akt pathway upregulation, which has anti-apoptotic effect in cardiomyocytes [26], corroborating data of Liao et al (2019) [27], which showed that IGF-1 can protect ischemic myocardium from ischemia/reperfusion injury by activating the PI3K/Akt pathway in vivo. Previous work demonstrated that mice lacking both insulin and IGF-1receptors in the heart displayed disrupted PI3K and Akt activity in cardiomyocytes, which contributed to cardiac failure and animal death [28].…”

Knockdown of Tripartite Motif 8 Protects H9C2 Cells Against Hypoxia/Reoxygenation-Induced Injury Through the Activation of PI3K/Akt Signaling Pathway

“…The PI3K/Akt signaling pathway is a conserved pathway to many aspects of cell growth and survival, in physiological as well as in pathological conditions 20 , 21 . Recent studies have identified that PI3K/Akt is crucial for limiting oxidative stress, proinflammatory, and apoptotic events in response to I/R stimuli 22 – 24 . It has been well documented that activation of PI3K/Akt is associated with decreased myocardial ischemic injury.…”

Dual Effect of Taxifolin on ZEB2 Cancer Signaling in HepG2 Cells

“…Finally, as a serine/threonine kinase, Akt alone mediates many different effects including cardioprotection, carcinogenesis, regulation of metabolism, expression of ABC transporters or vimentin via more than one hundred downstream effector molecules [ 54 , 55 , 56 , 57 ]. According to the literature, taxifolin can mediate Akt dephosphorylation that directly contributes to depletion of vimentin [ 57 , 58 ] as confirmed by experiments with the Akt inhibitor GSK690693 ( Appendix A , Figure A4 ).…”