Chronic activation of cardiac Atg-5 and pancreatic Atg-7 by intermittent fasting alleviates acute myocardial infarction in old rats

Abstract

Background Aging is associated with cardiovascular and metabolic changes, increasing the susceptibility to acute myocardial infarction (AMI). Intermittent fasting (IF) has a beneficial effect on the age-associated cardiovascular diseases. The present study was planned to investigate the possible protective effect of IF against acute AMI induced by isoproterenol (ISO) in old rats and its possible underlying mechanisms mediated by heart and pancreatic autophagy. Thirty Male Wistar rats were divided into four groups: adult; old; Old-ISO (rats subjected to AMI by ISO) and Old-F-ISO groups (rats were subjected to IF for 4 weeks and AMI by ISO). Results IF significantly increased the mRNA expression of cardiac Atg-5 and pancreatic Atg-7 in Old-F-ISO versus old and adult groups. This was associated with a significant decrease in serum troponin-I, serum creatine kinase (CK-MB), cardiac malondialdehyde and cardiac TNF-α, fasting plasma glucose, and HOMA-IR in Old-F-ISO compared to Old-ISO group. Also, IF significantly decreased the age-related overall and visceral obesity in Old-F-ISO versus old and Old-ISO groups. Histological studies revealed attenuation of the local inflammatory response in Old-F-ISO versus Old-ISO group. Pancreatic Atg-7 and heart Atg-5 were significantly increased in Old-ISO versus old rats. Conclusions IF protects against acute AMI in old rats, possibly, via chronic activation of heart Atg-5 and pancreatic Atg-7, and alleviation of age-related overall and visceral obesity. Thus, IF could be a dietary lifestyle modification for attenuation of the susceptibility to acute AMI in aged population. On the other hand, acute activation of heart and pancreatic autophagy by ISO might augment cardiac injury.

The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting

“…These features indicate that the activation of the lysosomal degradative machinery via autophagy following IF can exert regenerative outcomes in cardiac tissue with the occurrence of ischemic changes. Of note, active Atg5 expression and autophagic flux in starved cardiomyocytes contribute to resistance against ischemic conditions [ 92 ]. In aged rats subjected to acute myocardial infarction with isoproterenol, 4-wk IF led to upregulation of Atg5 and reduction of cardiac creatine kinase, MDA, TNF-α, and FBS [ 92 ].…”

“…Of note, active Atg5 expression and autophagic flux in starved cardiomyocytes contribute to resistance against ischemic conditions [ 92 ]. In aged rats subjected to acute myocardial infarction with isoproterenol, 4-wk IF led to upregulation of Atg5 and reduction of cardiac creatine kinase, MDA, TNF-α, and FBS [ 92 ]. Within hepatic tissue, autophagy function is very important due to its unique metabolic status and specific function [ 93 ].…”