The roles of subcellular Argonaute 2 in cardiovascular diseases

Argonaute 2 (Ago2), the core component of the microRNA-induced silencing complex (miRNA-RISC), is a pivotal protein with a well-established and potent role in gene expression regulation. Traditionally, Ago2 functions at the post-transcriptional level by binding to non-coding RNAs in the cytoplasm, facilitating gene expression via cleavage, deadenylation, or repression of target messenger RNA (mRNA) translation. Emerging evidence indicates that Ago2 can be transported from the cytoplasm to the nucleus or mitochondria, where it performs its critical functions. We observed that nuclear and mitochondrial Ago2 have been increasingly implicated in the pathogenesis of various cardiovascular diseases, such as hypertension, diabetic cardiomyopathy, and heart failure. These findings suggest a potential novel therapeutic strategy for targeting Ago2 in cardiovascular conditions. In this review, we aim to provide a comprehensive overview of recent studies elucidating the transport mechanisms of mammalian Ago2 into various subcellular organelles and summarise the functional roles and molecular mechanisms of subcellular Ago2 in cardiovascular diseases, offering a theoretical framework for Ago2-related therapeutic strategies.