Effects of myocardial ischemia/reperfusion injury on plasma metabolomic profile during aging

Background: Heart disease is a frequent cause of hospitalization and mortality for elderly patients. A common feature of both heart disease and aging itself is the involvement of metabolic organ alterations ultimately leading to changes in circulating metabolite levels. However, the specific contribution of aging and ischemic injury to the metabolic dysregulation occurring in older adults with ischemic heart disease is still unknown. Aim: To evaluate the effects of aging and ischemia/reperfusion (I/R) injury on plasma metabolomic profiling in mice. Methods: Young and aged mice were subjected to a minimally invasive model of I/R injury or sham operation. Complete evaluation of cardiac function and untargeted plasma metabolomics analysis were performed. Results: We confirmed that aged mice from the sham group had impaired cardiac function and augmented left ventricular (LV) dimensions compared to young sham-operated mice. Further, we found that ischemic injury did not drastically reduce LV systolic/diastolic function and dyssynchrony in aged compared to young mice. Using an untargeted metabolomics approach focused on aqueous metabolites, we found that ischemic injury does not affect the plasma metabolomic profile either in young or old mice. Our data also demonstrate that age significantly affects circulating metabolite levels (predominantly amino acids, phospholipids and organic acids) and perturbs several pathways involved in amino acid, glucid and nucleic acid metabolism as well as pyridoxal-5′-phosphate salvage pathway in both sham and ischemic mice. Conclusions: Our approach increases our understanding of age-associated plasma metabolomic signatures in mice with and without heart disease excluding confounding factors related to metabolic comorbidities.