Reading the Signature of Autophagy in the Ischemic and Infarcted Heart: A Systematic Review of Circulating Biomarkers

Ischemic heart disease is the main cause of death worldwide. Classic cardiac biomarkers, such as troponin, which are released due to myocyte necrosis, are widely used for diagnosis, but they provide limited information about the initial underlying cellular processes involved in myocardial infarction. Autophagy is now considered fundamental in the pathophysiology of cardiac ischemia and related reperfusion injury. This systematic review aims to identify and highlight candidate autophagy-related biomarkers in cardiac ischemia and infarction with potential benefits for early diagnosis, prognosis, and therapy. A comprehensive literature search was conducted up to 1 June 2025. We included studies that examined biomarkers involved in the autophagy process in cardiac ischemia/infarction, which involved humans and animal models. A total of 14 eligible articles were reviewed. Thirteen autophagy-related biomarkers were identified, including LC3-II/I, Beclin-1, ATG5, ATG7, p62, WIPI1, FGF21, CHRF, Rubicon, IL-1β, IL-18, and adiponectin. These biomarkers have a dynamic pattern, and they exhibited time-dependent changes during the different stages of myocardial infarction. Autophagy biomarkers present a promising understanding of the molecular mechanism of early myocardial ischemia and infarction. Integration of autophagy biomarkers with the classic markers should improve risk stratification, therapeutic decision-making, and prognosis in patients with ischemic heart disease.