Macrophage-associated noncoding RNAs in atherosclerosis and chronic kidney disease.

Although approximately 97% of the human genome does not encode proteins, it produces a vast repertoire of regulatory RNA transcripts that play critical roles in cellular and molecular processes. Among these, noncoding RNAs including microRNAs and long noncoding RNAs have emerged as key regulators of gene expression through their interactions with DNA, RNA, and proteins. Increasing evidence indicates that noncoding RNAs are central to immune regulation and inflammatory signaling, positioning them as important contributors to complex chronic diseases. Chronic kidney disease (CKD) is of particular interest because it represents a growing global health burden with strong inflammatory and metabolic overlap with cardiovascular disease, placing it at the center of cardio-kidney-metabolic disease. In both atherosclerosis and CKD, a pro-inflammatory milieu characterized by sustained macrophage accumulation and activation drives vascular dysfunction, organ ischemia, and progressive tissue injury. Macrophages act as pivotal instigators of these cardio-kidney-metabolic pathologies by integrating inflammatory signaling, lipid handling, and tissue remodeling processes. This review discusses current knowledge on the roles of noncoding RNAs in regulating macrophage function in atherosclerosis and CKD, with particular emphasis on the molecular mechanisms underlying inflammatory responses and disease progression. By highlighting shared and disease-specific noncoding RNA-mediated pathways, this review aims to provide insight into novel regulatory networks and potential therapeutic targets in cardio-kidney-metabolic disease.