Targeting FoxO1 in Cardiovascular Diseases: Mechanisms and Therapeutic Potential

Cardiovascular Disease (CVDs), as a major life-threatening disease, has attracted worldwide attention. Seeking novel and effective therapeutic strategies is still among the important in the cardiovascular field. Forkhead box O (FoxO) family comprises a group of transcription factors with highly conserved structures that have a major role in a plethora of biological functions. Recently, A considerable amount of research has shown the physiological and pathological roles of Fox family (especially FoxO1) in CVDs (ischemia-reperfusion injury, myocardial hypertrophy, myocardial infarction, myocardial fibrosis, cardiomyopathy, and atherosclerosis), and they affect the plasticity, stress response, and cardiac metabolism of the heart by regulating various signaling pathways and biological functions. In this review, we begin by outlining the structure of the Fox family and FoxO1. Next, we summarize the various pathological and physiological mechanisms of FoxO1 (including inflammation, oxidative stress, autophagy, endothelial dysfunction, lipid metabolism and angiogenesis), as well as the regulatory style of FoxO1 in the cardiovascular system (including phosphorylation, methylation, ubiquitination and acetylation). Finally, we also reviewed the latest research advancements and potential future research directions concerning FoxO1 regulators in CVDs, laying the foundation for its transformation into a new and powerful clinical application.