Time-dependent integrated tissue and circulating biomarker dynamics of spexin and progranulin in an experimental myocardial infarction model

Abstract Inflammation, oxidative stress and apoptosis, in particular, play critical roles in the pathophysiology of myocardial infarction (MI). Isoproterenol (ISO) is a frequently used agent in experimental models to induce MI. This study aimed to determine the temporal changes in Spexin (SPX) and Progranulin (PRG) levels in an ISO-induced experimental MI model. The study consisted of control and ISO-treated groups (ISO-1, ISO-2, ISO-4, ISO-6 and ISO-24). In the ISO-induced MI model, serum CK-MB and troponin (I-T) levels increased, confirming cardiac damage. However, increases in oxidative parameters and decreases in antioxidant enzyme levels indicated cardiac oxidative stress. Furthermore, the time-dependent increase in inflammatory cell infiltration on histopathological examinations, paralleled by the increase in proinflammatory cytokines, confirmed the cardiac inflammatory response. Despite a decrease in cardiac antiapoptotic markers, the increase in proapoptotic marker levels reflected the temporal change in the apoptotic process induced by ISO administration. ISO administration caused SPX levels in serum and cardiac tissue to increase at 4 h and decrease at 24 h. The dynamic fluctuations in SPX levels may be related to adaptation to the stress responses and cardiac energy metabolism. ISO administration increased PRG levels in serum and cardiac tissue at 6 and 24 h. This increase suggests that PRG may contribute to a role particularly in inflammation and cardiac remodeling processes. In conclusion, the cardiac oxidative stress, inflammation and apoptosis induced by ISO administration further validated the experimental MI model. Changes in SPX and PRG levels in the ISO-induced MI model demonstrate their promise as cardiac potential markers. Graphical Abstract