Acylated ghrelin protection inhibits apoptosis in the remote myocardium post-myocardial infarction by inhibiting calcineurin and activating ARC

Abstract

This study investigated if acylated ghrelin (AG) could inhibit myocardial infarction (MI)-induced apoptosis in the left ventricles (LV) of male rats and tested if this protection involves modulating ARC anti-apoptotic protein. Rats (n = 12/group) were assigned as a sham-operated, a sham + AG (100 µg/kg, 2x/d, S.C.), MI, and MI + AG. With no antioxidant activity or expression of FAS, AG inhibited caspase-3, 8, and 9 and decreased cytosolic/mitochondrial levels of cytochrome-c, Bax, Bad, and Bad-BCL-2 complex in the LVs of the sham-operated and MI-treated rats. Concomitantly, AG preserved the mitochondria structure, decreased mtPTP, and enhanced state-3 respiration in the LVs of both treated groups. These effects were associated with increased mitochondrial levels of ARC and a reduction in the activity of calcineurin. Overall, AG suppresses MI-induced ventricular apoptosis by inhibition of calcineurin, activation of ARC, and preserving mitochondria integrity.

Keywords:

• Ghrelin
• myocardial infarction
• ARC
• mitochondria
• apoptosis

Acknowledgements

The author extends their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through a research groups programme under grant number (R.G.P. 1/18/42). The author also extends the appreciation to Dr. Muhammad Alaa Eldeen for their efforts and help in this article.

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, Eid R.A. The data are not publicly available due to their containing information that could compromise the privacy of research participants.

Additional information

Funding

This work was supported by Deanship of Scientific Research at King Khalid University.