Circulating miRNAs Correlate With rIPC-Induced Cardioprotection and Its Impairment in Diabetic Myocardial Infarction via AMPK Signalling.

Remote ischemic preconditioning (rIPC) has shown potential in protecting myocardial tissue against acute myocardial infarction (AMI), primarily through anti-apoptotic, anti-inflammatory, and anti-hypoxic mechanisms. However, its effectiveness is compromised in the presence of metabolic comorbidities such as diabetes. Circulating microRNAs (miRNAs), which act as intercellular communicators, have been implicated in the systemic effects of rIPC, but their profiles and underlying mechanisms in diabetic conditions remain unclear. We constructed AMI models in both diabetic and non-diabetic rats and performed rIPC treatment. Plasma samples were collected for miRNA sequencing to identify differentially expressed circulating miRNAs. We observed that rIPC significantly altered the expression of several circulating miRNAs, including miR-19a-3p, miR-221-5p and miR-210-5p, which were associated with improved cardiomyocyte survival under ischemic conditions. Conversely, miR-34a-3p, miR-532-5p and miR-410-5p were found to be up-regulated in diabetic rats and were associated with enhanced cardiomyocyte apoptosis, inflammation and impaired rIPC efficacy. These miRNAs may be downstream of AMPK signalling, suggesting a potential molecular association between rIPC and metabolic status. This study identifies a panel of circulating miRNAs that are associated with the beneficial effects of rIPC and those that are linked to its impairment under diabetic conditions. Our findings highlight circulating miRNAs as candidate modulators that may influence myocardial responses under comorbid AMI. Nevertheless, the cellular source and upstream regulation of these miRNAs, as well as their effects on non-cardiac organs, warrant further investigation.